Ebm Sadari 2

CLINIC AL PRACTICE GUIDELINES
CLINIC AL PRACTICE GUIDELINES
Management of early
breast cancer
Management of early breast cancer
NHMRC
National Health &
Medical Research Council
Clinical practice guidelines for the
management of early breast cancer:
Second edition
Prepared by the iSource National Breast Cancer Centre
Endorsed August 2001
NHMRC
National Health &
Medical Research Council
Clinical practice guidelines for the management of early breast cancer i

© Commonwealth of Australia 2001
ISBN Print: 1864960876 Online: 1864960930
This work is copyright. Apart from any use as permitted under the Copyright
Act 1968, no part may be reproduced by any process without prior written
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Canberra ACT 2601. Email address: Cwealthcopyright@dofa.gov.au
The strategic intent of the NHMRC is to provide leadership and work with other
relevant organisations to improve the health of all Australians by:
• fostering and supporting a high quality and internationally recognised research

base;
• providing evidence based advice;
• applying research evidence to health issues thus translating research into better
health practice and outcomes; and
• promoting informed debate on health and medical research, health ethics and
related issues.
This document was prepared by the iSource National Breast Cancer Centre Early
Breast Cancer Working Group.
This document is a general guide to appropriate practice, to be followed only

subject to the clinician’s judgement and the woman’s preference in each
individual case.
The guidelines are designed to provide information to assist decision-making

and are based on the best information available at the time of publication.
This is the second edition of the Clinical Practice Guidelines for the
Management of Early Breast Cancer and replaces the first edition released in
1995.
It is planned to review this Clinical Practice Guideline by 2006. For further

information regarding the status of this document, please refer to the NHMRC
web address: http://www.nhmrc.gov.au
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ii Clinical practice guidelines for the management of early breast cancer

CONTENTS
For ew or d vii
List of abbr eviation s ix
Impor tan t n otice xi
In tr oduction 1
Summar y of guidelin es 7
1. Th e clin ical pictur e 11

1.1 Incidence and mortality 11
1.2 Risk factors in women 12
1.3 Genetics 15
1.4 Prognostic indicators in breast cancer 17
1.5 The impact of diagnosis and treatment on the woman 17
1.6 The effect on the family 18
2. Gen er al pr in ciples of car e 21

2.1 Aims of treatment 21
2.2 Establishing good communication practices 22
2.3 Counselling and support 29
2.4 Choosing a specialist 32
2.5 Second opinion 34
2.6 Disclosure of risk 34
2.7 Clinical trials 35
2.8 Pregnancy 37
2.9 Complementary and alternative therapies 38
3. Befor e defin itive tr eatmen t 41

3.1 History 42
3.2 Clinical examination 42
3.3 Investigations 43
3.4 Pathology 47
Clinical practice guidelines for the management of early breast cancer iii
4. Sur ger y for in vasive br east can cer 51
4.1 Breast conserving surgery 51
4.2 Total mastectomy 52
4.3 Comparison of breast conserving surgery with mastectomy 53
4.4 Management of the axilla 55
4.5 Breast reconstruction 60
4.6 External breast prostheses 61
4.7 Complications of surgery 62
4.8 The economics of locoregional therapy 65
4.9 Practice audit 65
5. Radioth er apy 67
5.1 Radiotherapy after breast conserving surgery 67
5.2 Radiotherapy after mastectomy 68
5.3 Complications of radiotherapy 71
6. Systemic adjuvan t th er apy 77

6.1 Pre-operative chemotherapy 78
6.2 Post-operative adjuvant chemotherapy 79
6.3 Tamoxifen 84
6.4 Ovarian ablation 87
6.5 Combined modalities 89
6.6 Which women should be offered systemic adjuvant therapy? 91
6.7 Recommendations 92
6.8 The economics of systemic adjuvant therapy 95
7. Follow -up 97
8. Requir emen ts for special gr oups 1 03

8.1 Women from rural and remote areas 103
8.2 Cultural issues 104
9. Ar eas w h er e r esear ch is n eeded 1 07
iv Clinical practice guidelines for the management of early breast cancer

Appen dices
A. Development of the first edition (1995) 111
B. Revision of the first edition (1995) and production of
the second edition (2001) 121
C. TNM clinical classification 139
D. RACOG Bulletin Vol 10, No 1, May 1996 (working party on
tamoxifen and the endometrium) 141
E. Questions you may be asked 145
F. iSource National Breast Cancer Centre Publications List 149
G. Types of clinical trials 153
H. Breast cancer support services 155
I. RACS Breast Audit 161
Glossar y 1 63
Refer en ces 1 85
List of tables
1. Recommendations for management of the axilla 59
2. Chemotherapy: effect on outcome 79
3. Tamoxifen duration: effect on outcome 85
4. Efficacy of adjuvant ovarian ablation in women under 50 years 88
5. Definition of risk categories for patients with node-negative
breast cancer 93
6. Systemic adjuvant therapy recommendations outside clinical trials 94
7. Recommended follow-up schedule 101
8. Classification of clinical trials (Appendix G) 154
List of figur es
1. Age-standardised incidence rates of breast cancer by age in
women in Australia, 1982–1996 11
Clinical practice guidelines for the management of early breast cancer v

F O R E WO R D
In October 1995 the National Health and Medical Research Council released the
Clinical practice guidelines for the management of early breast cancer. These
guidelines were the first in the NHMRC’s new program and they represented a
landmark in evidence-based medicine in Australia.
The guidelines were based on a review of the available evidence about the
management of breast cancer and were developed by a multidisciplinary team. In
the six years since their launch, the guidelines were very well received by
clinicians and were viewed by women as an important resource in understanding
their treatment choices.
Commencing in December 1998, the iSource National Breast Cancer Centre
undertook a revision of these guidelines. Ongoing review is vital if the guidelines
are to remain a good summary of the most recent research. Our understanding of
breast cancer management has moved forwards since 1995 and this is reflected in
the revised guidelines.
Breast cancer remains a major health issue for Australian women, with 10,000
new cases diagnosed each year. I am confident that the guidelines will continue
to make a significant contribution to ensuring that all women diagnosed with
early breast cancer receive care based on the best available evidence.
Professor Christine Ewan

Chair
Board
iSource National Breast Cancer Centre
Clinical practice guidelines for the management of early breast cancer vii
L I S T O F A B B R E V I AT I O N S
ADH atypical ductal hyperplasia

AH atypical hyperplasia
ALH atypical lobular hyperplasia
BCSS Breast Cancer Support Service
CA 15.3 breast cancer tumour marker
CEA non-specific tumour markers
CLE complete local excision
CMF cyclophosphamide, methotrexate and 5-fluorouracil
CS conservative surgery
CSF colony stimulating factor
DCIS ductal carcinoma in situ
EIC extensive intraductal carcinoma
EORTC European Organization for Research and Treatment of Cancer
ER oestrogen receptor
FAC 5-fluorouracil, doxorubicin and cyclophosphamide
FNAB fine-needle aspiration biopsy
G-CSF granulocyte colony stimulating factor
GP general practitioner
Gy Gray
HRT hormone replacement therapy
IBT ipsilateral breast tumours
LCIS lobular carcinoma in situ
LHRH luteinizing hormone releasing hormone
NBCC/ iSource National Breast Cancer Centre
the Centre
NHMRC National Health and Medical Research Council
NSABP National Surgical Adjuvant Breast and Bowel Project
PgR progesterone receptor
QALY quality adjusted life year
QCHOC Quality of Care and Health Outcomes Committee
Clinical practice guidelines for the management of early breast cancer ix

RCT randomised controlled trial
RR relative risk
SD standard deviation
TRAM transverse rectus abdominis myocutaneous
UICC Union Internationale Contre le Cancer (International Union Against
Cancer)
x Clinical practice guidelines for the management of early breast cancer

I M P O RTA N T N OT I C E
This document is a guide to appropriate practice, to be followed subject to the

clinician’s judgement and the woman’s preference in each individual case.
The guidelines are designed to provide information to assist decision making and
are based on the best evidence available at time of publication.
Clinical practice guidelines for the management of early breast cancer xi

INTRODUCTION
D E F I N I T I O N O F E A R LY B R E A S T C A N C E R
These guidelines refer to breast cancer in the early stages, as it commonly

presents. Early breast cancer has been defined as tumours of not more than five
centimetres diameter, with either impalpable or palpable but not fixed lymph
nodes and with no evidence of distant metastases.This corresponds to tumours
that are T1-2, N0-1, M0 as currently defined by the International Union Against
Cancer (UICC).1 Please refer to Appendix C for further details.
PURPOSE OF THE GUIDELINES
Clinical practice guidelines for the management of early breast cancer aims to
be a document useful for both health professionals and consumers. It is designed
to:
• assist women and their doctors in decision making
• educate all involved in the care of women with breast cancer
• assess and assure the quality of care
• reduce the risk of legal liability by improving care
• bring the issue of cost-effectiveness into the public arena.
This book presents guidelines; it does not pretend to be a textbook. Clinicians
looking for further information on the biology and natural history of breast
cancer should consult the relevant texts.
These guidelines are neither rigid procedural paths, nor prescriptive. They aim to
provide information on which decisions can be made, rather than dictate what
decisions should be.2
Clinical practice recommendations are boxed as ‘Guidelines’ throughout the text
and are summarised at the beginning under ‘Summary of Guidelines’.These are all
evidence-based and the level of evidence is clearly denoted.
There are also boxed ‘Key points’ to draw the reader’s attention to other issues of
importance.These are not clinical practice recommendations. Some are based on
evidence derived from different studies (not necessarily Level I), while others
refer to areas for which there is no ‘hard’ evidence but which were considered by
the working group as important for clinicians to note.
Clinical practice guidelines for the management of early breast cancer 1

L E V E L S O F E V I D E N C E R AT I N G S
The guidelines use a four-level rating system to enable the reader to identify the
strength of the evidence base for key decision points.This rating system is
recommended by CHOC2 and has been adapted from the system developed by
the US Preventive Services Task Force. The system is as follows:
Level I Evidence is obtained from a systematic review of all relevant
randomised controlled trials.
Level II Evidence is obtained from at least one properly designed randomised
controlled trial.
Level III Evidence is obtained from well designed controlled trials without
randomisation; OR from well designed cohort or case control analytic
studies, preferably from more than one centre of research group; OR
from multiple time series with or without the intervention.
Level IV This represents the opinions of respected authorities based on
clinical experience, descriptive studies or reports of expert
committees.
The guidelines are based on reviews of the available evidence. They have also
been informed by recommendations of expert groups. While Level I evidence
represents the gold standard, it is not available for all areas of practice and for
some recommendations the working party considered it appropriate to base
recommendations on other levels of evidence.
These guidelines summarise areas of knowledge, but also highlight areas where
knowledge is inadequate. This will provide guidance for research. The guidelines
will continue to be evaluated to determine their degree of use by practitioners
and their effects on patient outcomes.
Appendix B details the process for the development and evaluation of these
guidelines.
N H M R C C L I N I C A L P R AC T I C E G U I D E L I N E S F O R T H E
M A N A G E M E N T O F E A R LY B R E A S T C A N C E R
First edition (1995)

In 1993 the National Health and Medical Research Council (NHMRC), through its
Standing Committee on Quality of Care (now the Standing Committee on Quality
of Care and Health Outcomes (QCHOC)), established a working party to develop
clinical practice guidelines for the management of breast cancer.
This was part of the national program to promote the development of evidence-
based clinical practice guidelines, which was aimed at improving the quality of
health care and patient health outcomes.
2 Clinical practice guidelines for the management of early breast cancer

Breast cancer was chosen as a suitable topic because of concerns that knowledge
of the treatment options was not well disseminated among health professionals,
and that not all women with breast cancer were being presented with the range
of appropriate treatment options. All women deserve access to advice and care of
the best known standard.
QCHOC established a working party comprised of representatives from breast
surgery, radiology, education, pathology, the consumer movement, medical
oncology, radiation oncology, reconstructive surgery, counselling and support
staff, nursing, general practice, research and psychiatry.The full list of members
and the terms of reference of that working party are shown in Appendix A.
The guidelines were based on a number of reviews of the evidence. The
outcomes of the Consensus Development Conference 3,4-6—conducted in June,
1994 under the sponsorship of the Clinical Oncological Society of Australia, the
Australian New Zealand Breast Cancer Trials Group, the Medical Oncology Group
of Australia and the Breast Section of the Royal Australasian College of Surgeons—
also gave a sound basis on which to begin the development of the guidelines.
The report from the NHMRC women’s sub-group was also important in drafting
the guidelines.7 That report was commissioned by QCHOC at the request of the
working party, which reviewed all available consumer literature regarding
women’s experiences of breast cancer.
The first edition (1995) of the guidelines was the result of the deliberations of
the working party considering all of the available evidence. They were endorsed
by the NHMRC and first released in October 1995.
The guidelines were well received by clinicians. For example, in a survey of 150
randomly selected surgeons, 97 per cent believed the guidelines were a good
summary of the most recent evidence; 96 per cent reported that they were easy
to understand; 86 per cent felt that they would assist in reaching agreement
between clinicians and women; and 85 per cent believed that they would be
useful in improving management.8 Many clinicians believed that their practice
was already consistent with the guidelines.8,9
Subsequent to the release of the guidelines, there has been considerable work by
the iSource National Breast Cancer Centre, professional colleges and health
authorities at the national, state and local level to foster their adoption. The
guidelines have been the subject of much continuing medical education and are
available on the Internet (www.nbcc.org.au). Current practice has been explored
and the use of routine data audit fostered. Special initiatives have been directed at
areas of concern, including the medico-legal consequences of the guidelines and
multidisciplinary care in rural areas.10 A condensed guide (The management of
early breast cancer for general practitioners)11 has been produced for general
practitioners, focusing on those aspects most relevant to primary care providers.

Second edition (2001)
In keeping with NHMRC recommendations, the guidelines have been reviewed
and updated to provide a new edition for 2001 onwards.
The steps taken in reviewing the guidelines were as follows:
• A review of the scientific findings on which the original guidelines were
based was completed by the Cochrane Collaborative Review Group in
Breast Cancer.The update was conducted in December 1996 and repeated
in December 1997. The accuracy of the statements in the guidelines, the
supporting references and the levels of evidence were reviewed.
• Several new reviews of evidence have been completed by the iSource
National Breast Cancer Centre and other agencies. The results of these
analyses have been incorporated into the 2001 edition; a list of reviews
conducted for the revision of the guidelines is included in Appendix B. In
particular, detailed reviews about the psychosocial aspects of care 12,13
enabled a more detailed discussion of these issues in this second edition of
the guidelines.
• Feedback on the first edition of the guidelines was sought at the end of
1997 and the beginning of 1998 from a broad range of agencies involved in
Blank
breast cancer control. A facing page
list of the to introduction
organisations consulted is included in
Appendix B. Comments from these organisations were reviewed by the
working group which developed the 1995 edition of the guidelines.
• A sub-group of the original working group was established to provide a
detailed review of the first edition of the guidelines. The sub-group
comprised of Emeritus Professor Tom Reeve (Chair), Associate Professor
Alan Coates, Mr Colin Furnival, Professor Allan Langlands (member until
April 2000) and Ms Jayne Ross.
Further review and redrafting was undertaken in the particular areas detailed in
Appendix B. Literature was included up until mid-2000.
For information on the management of advanced breast cancer, the reader is
referred to the Clinical practice guidelines on the management of advanced
breast cancer, 2001.
The consumer version

At the same time as the 1995 edition of the guidelines was released, NHMRC
published a version of the guidelines for women with early breast cancer and
their families (A consumer’s guide: early breast cancer).14 The NHMRC
recommends that doctors inform their patients of the availability of this book,
and that they recommend it as a reference to be used in cooperation with their
doctor and other health carers with whom they are involved.

Subsequently, the iSource National Breast Cancer Centre reproduced this
document in a simpler format (All about early breast cancer).15 Both documents
have been viewed very positively by women, and in a recent survey it was found
that two-thirds of women diagnosed with early breast cancer now receive a copy
of one of these documents.16
A revised version of these consumer resources, consistent with this second
edition of the clinical practice guidelines, will be released.
Further information resources are available from the iSource National Breast
Cancer Centre. All about early breast cancer is available on audiocassette and
has been translated into Italian, Greek, Arabic and Chinese. A CD-ROM program
based on these guidelines is also available so women can access this information
interactively.
Clinicians are encouraged to promote the use of the consumer version of these
guidelines and discuss them with the woman as required.

S U M M A RY O F T H E G U I D E L I N E S
The following table provides a summary of the guideline recommendations

presented in this document. All of the recommendations should be considered in
the care and management of women with early breast cancer. Readers should
turn to the appropriate chapters to understand each recommendation in context
of the evidence.
Guidelines Level of References Chapter

evidence
COUNSELLING AND SUPPORT

1. Providing women with support and detailed I 120–122 2.2
information about their diagnosis and treatment
increases their emotional wellbeing and assists
their physical and emotional recovery.
2. Strategies to improve recall of information are

recommended, including: II 116–119 2.2
• the provision of a breast care nurse or
counsellor
• tape recording of the consultation
• follow-up letter
• psycho-educational programs
3. Counselling is recommended for women with I 120 2.3

breast cancer, as it improves quality of life.
4. The involvement of a breast care nurse in the II 79, 116, 123 2.3
treatment team is recommended, as this reduces
psychological morbidity.
PARTICIPATION IN CLINICAL TRIALS

5. There is indirect evidence that women who III 136–138 2.7
participate in clinical trials have better outcomes
than similar women given similar treatment
outside trials.
MULTIDISCIPLINARY CARE
6. The outcome of patients with breast and other III 134 3
cancers is better if they are treated by a clinician
who has access to the full range of treatment
options in a multidisciplinary setting.
evidence
SURGERY FOR INVASIVE BREAST CANCER

7. In discussion of the choice between breast I 207 4.3
conserving surgery and mastectomy, women
should be informed that body image is better
preserved with conservation surgery.
8. Where appropriate, women should be offered a I 195 4.3

choice of either breast conserving surgery
followed by radiotherapy or mastectomy, as there
is no difference in the rate of survival or distant
metastasis.
9. For most women with early breast cancer, a

level 1 or level 2 axillary node dissection II 205, 217 4.4
should be standard.
RADIOTHERAPY
10. Radiotherapy after complete local excision (CLE) I 195, 260, 266 5.1
is recommended as it significantly reduces the
risk of local recurrence in the breast and the need
for further surgery. It should not be omitted, even
in selected patients.
11. Postmastectomy radiotherapy is recommended I 269, 228 5.2

for women at high risk of local or regional relapse.
SYSTEMIC ADJUVANT THERAPY

12. Under the age of 50 years (pre-menopausal I 299 6
women), ovarian ablation reduces the risk of
recurrence and death for women with breast
cancer (see Chapter 6,Table 4).
13. Up to the age of 70 years, multi-agent I 298 6

chemotherapy reduces the risk of recurrence and
death for women with breast cancer
(See Chapter 6,Table 6).

evidence
SYSTEMIC ADJUVANT THERAPY con’t

14. Moderately prolonged (several months) combined I 295 6.2
chemotherapy is recommended as it is more
effective than single agent therapy and than
treatment lasting less than one month.
15. Anthracycline-containing regimes are superior to I 298 6.2

cyclophosphamide, methotrexate and 5-fluoro-
uracil (CMF) for both recurrence-free survival and
overall survival at the increased risk of alopecia,
cardiac toxicity and febrile neutropenia.
16. Dose intensity is important to outcome in II 311 6.2

adjuvant cytotoxic therapy, at least in dose ranges
achievable without colony stimulating factor (CSF)
support.
17. Treatment with high-dose chemotherapy outside II 314, 315 6.2

of clinical trials is not recommended.
18. Women should be fully informed of the short- and III 333 6.2
long-term effects of cytotoxic chemotherapy on
general functioning and on body image,
sexuality and fertility.
19. Tamoxifen is recommended for most women with I 297 6.3

oestrogen receptor positive tumours, as it
significantly improves recurrence-free and overall
survival in women of all age groups.
20. Tamoxifen reduces the incidence of contralateral I 297 6.3

breast cancer.
21. Women should be informed of the potential side II 45–48 6.3

effects of tamoxifen, including endometrial cancer,
stroke, pulmonary embolism, deep vein
thrombosis, hot flushes and vaginal dryness and
discharge, but not excess weight gain. For most
women, the protective effect of tamoxifen against
the recurrence of breast cancer will vastly
outweigh the increased risk of side effects.

evidence
SYSTEMIC ADJUVANT THERAPY con’t

22. Ovarian ablation is more effective in women with II 300 6.4
oestrogen receptor positive tumours.
COMBINED MODALITIES
23. Chemotherapy in combination with tamoxifen I 352 6.5
yields an increase in disease-free survival
compared with tamoxifen alone.
24. Tamoxifen in combination with chemotherapy I 297 6.5

yields an increase in disease-free survival
compared with chemotherapy alone.
FOLLOW-UP
25. A minimal follow-up schedule is recommended, II 365, 366 7
as there is no evidence that frequent intensive
follow-up confers any survival benefit or
increase in quality of life.
Papers prepared by the iSource National Breast Cancer Centre are available from the Centre by contacting
their publications voicemail service on (02) 9334 1882 or 1800 624 973.

CHAPTER 1 THE CLINICAL PICTURE
1 . 1 I N C I D E N C E A N D M O RTA L I T Y
Incidence
In Australia in 1996, 9,556 women were diagnosed with breast cancer.17 The
incidence of breast cancer has been increasing by between 1–2 per cent per
annum for the past decade; however, there is some evidence that this increase
may not continue.18 The incidence of breast cancer increases with age (see
Figure 1).19
Figure 1: Age-standardised incidence rates of breast cancer

by age in women in Australia, 1982–1996
Source: Australian Institute of Health and Welfare, Australasian Association of Cancer Registries and
NHMRC National Breast Cancer Centre 1999. Breast cancer in Australian women 1982–1996.
Canberra: AIHW (Cancer Series).

Mortality
Age-standardised rates have remained stable, at around 25–27 deaths per 100,000
woman-years between 1982 and 1996.20
Survival
The report Breast cancer survival in Australian women 1982–1994 showed
that five-year relative survival in Australian women of all ages increased from
74.4 per cent in 1982–1987 to 78.9 per cent in 1988–1992.21 Survival was best in
women aged in their 40s and poorer for women aged 80 years and over and
under 30 years of age.21
1 . 2 R I S K FAC TO R S I N W O M E N
The most important demographic risk factor for breast cancer is increasing age.21
A family history of breast cancer in first degree relatives, especially if the breast
cancer was bilateral or diagnosed at an early age, strongly increases the risk of
developing the disease, as discussed on the following pages.22
The reproductive factors which most strongly influence a woman’s risk of breast
cancer are the determinants of her menstrual life and her childbirth history.23-25
These facts, combined with substantial evidence from experimental, clinical and
epidemiological research, are taken to indicate that hormones play a major role in
the aetiology of breast cancer.25 The risk of breast cancer is increased while a
woman is taking the oral contraceptive pill, although the effect of the pill on
lifetime risk of breast cancer is small because risk of breast cancer is low at ages
when women commonly take the pill.26 Hormone replacement therapy (HRT)
after the menopause also appears to increase risk by about 30 per cent.27 The
excess risk increases with increasing duration of use, but disappears within about
2 years of stopping use.
There is emerging evidence that a number of other factors may make a minor
contribution to the aetiology of breast cancer.These include:
• high-energy intake and growth rate in childhood and adolescence (the risk
may be reduced by high intake of fruit and vegetables at any age)28
• a substantial increase in body size in post-menopausal women29,30
• alcohol (a daily intake of more than two drinks)31,32

Ductal carcinoma in situ, lobular carcinoma in situ and atypical
hyperplasia
Some breast diseases, including ductal carcinoma in situ (DCIS), lobular
carcinoma in situ (LCIS) and atypical hyperplasia (AH), are associated with an
increased risk of invasive breast cancer.33,34
DCIS is defined as an abnormal proliferative condition of epithelial cells in the
mammary ducts.These cells display cytological features of malignancy, but unlike
invasive cancer DCIS is confined within the ducts.The clinical significance of
DCIS lies in the proportion of DCIS lesions which will eventually develop into
invasive carcinoma. Historical data suggest that 20–30 per cent of untreated DCIS
will progress to invasive cancer (Level III).35-37
More recent studies also show a high frequency of invasive cancer after surgical
excision of DCIS. In a report of mammographically-detected DCIS, invasive cancer
occurred in 13 per cent of women within eight years of complete surgical
excision of intermediate to high-grade DCIS.38 This represents a ten-fold risk
compared with recent incidence figures.
Although there are no reliable predictors for probability of progression to
invasive carcinoma, the risk may be greater when DCIS displays features such as
comedo necrosis or high nuclear grade.39 On the other hand, in some cases
invasion may never occur, presumably due to arrest of the genetic changes which
lead to invasive cancer.40
As the natural history is largely unknown, special consideration of the
management of DCIS is required. As a general principle, small mammographically
detected lesions should be treated by complete local excision, with preservation
of the breast. In cases where the disease is extensive, total mastectomy may be a
more reliable treatment. Randomised controlled trials demonstrate a reduction in
DCIS recurrence and invasive breast cancer if radiotherapy is performed after
local excision for DCIS (Level II).38,41,42 Axillary lymph node dissection is not
necessary in the management of most patients with DCIS.43 Chemotherapy has
never been investigated or used in the treatment of DCIS. Recent evidence
indicates that the use of tamoxifen in women with DCIS in the adjuvant setting
reduces the risk of DCIS recurrence and invasive breast cancer (Level II).44
Women should be informed of the potential side effects of tamoxifen.45-48
The natural history of lobular carcinoma in situ (LCIS) is unclear. However, even
though little is known about the sequence of events leading from LCIS to invasive
carcinoma of the breast, the clinical importance of LCIS is the increased risk of
breast cancer associated with a diagnosis of LCIS. LCIS is a non-invasive
multicentric proliferation of the epithelial cells in the lobules and terminal ducts
of the breast. The relative risk of invasive breast cancer among women with a
diagnosis of LCIS is estimated to be in the order of 7–9 over 15 years (Level
III).49-52 The absolute risk of developing invasive breast cancer among women

with a diagnosis of LCIS is approximately 17 per cent over 15 years, and applies
to both the involved and uninvolved breast (Level III).49
There is limited evidence available to determine the management of women
diagnosed with LCIS as the only abnormality following a surgical breast biopsy.
Close surveillance, including frequent clinical examination and bilateral
mammography, supplemented by ultrasound if indicated, appears to be the best
management option currently available.
Atypical hyperplasia (AH) refers to the proliferation of atypical cells in the breast
epithelium. AH has been further sub-classified into atypical ductal hyperplasia
(ADH) and atypical lobular hyperplasia (ALH). The cells in ADH are similar to
those in DCIS, but the degree of involvement of the ducts and ductules is less
extensive. Similarly, the cells composing ALH are similar to those that characterise
LCIS, but the degree of involvement of the terminal ducts and lobules is less
extensive. Ductal lesions (DCIS and ADH) and lobular lesions (LCIS and ALH) are
usually regarded as representing continuums of abnormality which can eventually
lead to invasive cancer. The relative risk of breast cancer for women with AH has
been estimated to be three to four times that of the general population (Level
III).53,54 The relative risk increases to approximately nine when AH is associated
with a family history of breast cancer in a first-degree relative compared to
women with non-proliferative benign breast disease and no family history (Level
III).53 Furthermore, the risk of invasive breast cancer seems to be greatest in the
first ten years after diagnosis of AH.55 Annual physical examination and annual
bilateral mammography, supplemented by ultrasound if indicated, appears to be
the best management option currently available to women who are diagnosed
with AH as the sole abnormality following a breast biopsy.
(Clinical practice guidelines on the management of DCIS, LCIS and AH are
currently being prepared by the iSource National Breast Cancer Centre.)
Key points
In some cases of DCIS, invasion may never occur. This may be
the result of interruption of the genetic changes which lead to
invasive carcinoma.
Radiotherapy should be considered for women with DCIS
where conservation is desired.
Axillary lymph node dissection is not necessary in the
management of most patients with DCIS.
For women with LCIS and AH, annual physical examination and
annual bilateral mammography appears to be the best
management option.

1.3 GENETICS
(Please refer to iSource National Breast Cancer Centre Advice about familial
aspects of breast cancer and ovarian cancer: a guide for health professionals
(2000) for more details on family history and risk of breast cancer.)
A history of breast cancer in other relatives may mean that a woman has an
increased risk of breast cancer.22
In the last few years several genes associated with a high risk for breast cancer, in
particular BRCA1 and BRCA2, have been discovered. In the general population,
about 1 in 1000 women have inherited a mutation in one or other of these genes
which increases their risk of breast cancer at least 8–9 fold. BRCA1 and BRCA2
mutations explain only 1–2 per cent of all breast cancer.56 These mutations can be
transmitted through either the maternal or paternal lines.
It is now technically possible to determine whether a person has inherited some
BRCA1 or BRCA2 mutations. With current technology, it is not possible to detect
every mutation and only a few Australian laboratories can conduct this specialised
testing. Genetic testing raises complex medical and ethical issues, and should only
be offered with pre- and post-test counselling in conjunction with a specialist
genetics service for breast cancer.These issues are discussed in the Australian
Cancer Network’s Familial aspects of cancer. A guide to clinical practice.57
Evidence-based recommendations about categorising risk based on family history
are outlined in the National Breast Cancer Centre’s Advice about familial aspects
of breast cancer and ovarian cancer: a guide for health professionals (2000),58
along with recommendations about the appropriate management of women in
different risk groups.
This guide categorises women into three risk levels: women at or slightly above
the average risk; women at a moderately increased risk; and women at a
potentially high risk.
Women fall into the moderately increased risk category if:
• one or two first degree relatives were diagnosed with breast cancer before
the age of 50 (without the additional features of women at potentially high
risk described below)
OR
• two first or second degree relatives on the same side of the family,
diagnosed with breast or ovarian cancer (without the additional features of
women at potentially high risk described below)
Fewer than 4 per cent of women are in the moderately increased risk category,
and their lifetime risk of developing breast cancer is 12–25 per cent.They should
be advised to discuss any concerns with their general practitioner (GP).

Women at a potentially high risk due to their family history have about a 1 in 3
chance of belonging to a family in which a high risk mutation is causing cancer.
This includes those women who have:58
• three or more first or second degree relatives on the same side of the family
with breast or ovarian cancer
OR
• two or more first or second degree relatives on the same side of the family
with breast or ovarian cancer including any of the following high risk
features:
• diagnosis at age 40 or younger
• bilateral disease
• breast and ovarian cancer in one individual
• breast cancer in a male
• Jewish people of Ashkenazi origin.
Fewer than 1 per cent of women will be categorised as at high risk. Even in this
high risk group, 50–75 per cent of women will not develop breast cancer. The
lifetime risk on average of women in this category is between 25 per cent and
50 per cent but may be as high as 80 per cent in those women who have a high-
risk mutation. Women in this category should be offered appropriate clinical
surveillance.
If a woman with the above characteristics wishes to clarify her genetic risk or that of
her family, health professionals should discuss referral to specialist genetic services
for advice, appropriate counselling and management.A list of specialist genetic
services for breast cancer is available from the iSource National Breast Cancer Centre,
and can also be accessed through its website, http://www.nbcc.org.au
If a major intervention such as a bilateral mastectomy is planned—because of a
very strong family history or when a woman is found by genetic testing to have
inherited a mutated copy of a high risk gene, such as BRCA1 or BRCA2—a
second opinion is recommended before any final therapeutic decisions are made.
Information is available for women about these issues from the iSource National
Breast Cancer Centre in the booklet Breast cancer and family history: what you
need to know 59 and also from state and territory cancer organisations.
In most major Australian cities, family cancer clinics have been established with
the aim of providing individuals with information about familial aspects of cancer
and their risk of developing breast cancer associated with family history, and they
may also offer genetic testing where appropriate. Guidelines for national best
practice for family cancer clinics are available from the iSource National Breast
Cancer Centre.60

1 . 4 P RO G N O S T I C I N D I C ATO R S I N B R E A S T C A N C E R
Factors generally associated with a less favourable prognosis are:

• increasing tumour size61,62
• higher grade62-65
• the presence and number of lymph node metastases61
Factors associated with less favourable prognosis among node negative disease
are:66-68
• increasing tumour size
• increasing histological grade
• oestrogen-receptor negative
• progesterone-receptor negative
1 . 5 T H E I M PAC T O F D I A G N O S I S A N D T R E AT M E N T O N
T H E WO M A N
The diagnosis of breast cancer and its subsequent treatment may have a
significant impact on a woman’s body image, self-esteem, sexuality and
relationships.12,69-71 The impact may be greater with more intensive management,72
although there is not always a correlation between the emotional impact of
cancer and the severity of the disease and treatment. The psychological impact of
breast cancer may last long after the diagnosis is made.73
Many women who have breast cancer, like many people with any form of cancer,
feel helpless and powerless in the face of the disease.72 In addition to the threat
to their life, the diagnosis may:
• threaten their femininity
• be seen as a threat to their family
• cause worry over whether the cancer has spread
• lead to ongoing uncertainty over the future, which has an impact on
relationships, children, employment and many other parts of life
• lead to ongoing uncertainty over a whole range of issues, including what to
do about treatment
• produce a fear of being stigmatised and rejected once the diagnosis is
known74
The diagnosis and treatment of breast cancer may have a substantial impact on
the ability of the woman to continue with her normal daily life. The cancer and/
or the treatment may interfere with aspects of her life including work, sports,
sexual relationships, housework and caring for children.7

The treatment of breast cancer may have a significant financial impact on the
woman and her family, due to time off paid work and medical and other
expenses.7
Women will have different concerns at different times during diagnosis, treatment
and after the active treatment phase.They face important and often complex
decisions at each stage.75 They may wish to make decisions after discussion with
their doctor and nurses, or with their families.
Stressful times will vary with different circumstances for different women. They
occur most commonly at:
• the time of diagnosis
• awaiting biopsy results
• the period after diagnosis while waiting for treatment
• any prolonged wait for treatment
• the period following discharge from hospital—both immediately after, then
four to six weeks later
• the period following completion of treatment
All women react differently and deal with their cancer and its treatment
differently. All will find their mood and ability to deal with the situation fluctuates
with time.
Some women will experience more emotional difficulties than others. Women
may be more vulnerable to adverse outcomes, including anxiety and depression, if
they are younger, single, separated, divorced, widowed, economically
disadvantaged or have poor social support or poor marital/defacto/partner
relationships. Also included in the high risk group are women who have a past
history of psychiatric illness, cumulative stressful life events or poorer physical
health.76-78 Sexual, social and cultural factors will also modify morbidity.
A proportion of women will become clinically depressed following a diagnosis of
breast cancer. It is estimated that at three months post diagnosis 10–17 per cent
of women will be clinically depressed.79,80
The patient’s ethnic background and level of understanding of the English
language is critical. Referral to a professional medical interpreter is recommended
as appropriate.
1 . 6 T H E E F F E C T O N T H E FA M I LY
The impact of breast cancer may be profound not only for the woman affected,
but also for her family.81 Family members of newly diagnosed cancer patients
report high levels of concern and psychological distress (Level IV),82 and for
spouses of women with breast cancer the level of distress are comparable to the

woman’s (Level IV).83 The impact on children depends on their developmental
stage, and there is a need for each member of the family to have information
appropriate to their level of understanding (Level III).84
Family reactions play a key role in the coping of the woman, and promotion of
more open communication and expression of feelings is generally helpful in
adjustment (Level III).81 Lack of support from family and friends may be
associated with poorer emotional adjustment (Level III; Level IV).85-90
Furthermore, not all women are members of a traditional family unit. For these
reasons, it is important that key supportive relationships are identified for these
women.91-93 In some instances, the family or individual members may benefit from
referral for counselling.
(For further information refer to: NHMRC iSource National Breast Cancer Centre
Psychosocial clinical practice guidelines: providing information, support and
counselling for women with breast cancer, 2000).94

CHAPTER 2 GENERAL PRINCIPLES OF CARE
2 . 1 A I M S O F T R E AT M E N T
The primary goal in the treatment of early breast cancer is to control disease with
the aim of achieving cure.
There are various other desirable outcomes for treatment, including:
• to improve survival
• to minimise the risk of distant recurrence
• cosmesis
• the return to a quality of life as close as possible to the life before diagnosis
• relief of symptoms
When contemplating the aims of treatment, the woman and her doctor—and, if
desired, the woman’s family—should discuss the options in the realisation that
the initial management of breast cancer offers the best hope of cure. There is no
evidence that cure is possible after recurrence of breast cancer.
Key point
As there is no evidence to suggest that recurrent breast cancer
can be cured, (with the exception of in-breast recurrence after
breast conservation surgery), it is important to select the most
effective treatment from the outset.
Health professionals should be aware of which forms of management of breast

cancer have been shown to be effective and which ones have not.That
knowledge should be made available to women with breast cancer in a form
appropriate to each woman’s educational level and culture.95,96
The choice to proceed with treatment, and the choice of which form of
treatment, should be made by the woman after discussion with her doctor and
any others she may care to consult.97 The doctor is only entitled to decide which
form of treatment to pursue if the woman expressly delegates her decision to the
doctor. The doctor is not obliged to undertake a form of treatment with which he
or she does not agree.

Key point
There are significant individual differences in women’s views
about, and needs for, information, choice and support. In the
absence of research assisting health professionals to predict the
needs of individual women, these differences are best
accommodated by creating an environment in which each
woman can secure a level of information, autonomy and
support that suits her needs (Level III).98,99
As well as correct surgical or medical treatment, good management requires

attention to all factors that play some part in the management plan, such as:
• respecting dignity, privacy and confidentiality
• treating the woman as a whole person rather than as a host for a cancer
• acknowledging and accommodating if possible, a woman’s work and family
responsibilities
• minimising waiting times for appointments, treatments and results
• giving attention to amenities such as waiting areas7
2 . 2 E S TA B L I S H I N G G O O D C O M M U N I C AT I O N P R A C T I C E S
The way a clinician relates and communicates with a woman with breast cancer
will have an impact on her wellbeing.
Women need to be accurately and fully informed about their disease and
treatment options, so that they can understand both the nature of the threats to
be faced and the available support and treatment for breast cancer. Effective
communication involves more than the provision of information; it involves
explanation, problem solving and acknowledgment of feelings. Improved
psychological adjustment, decision-making, treatment compliance and satisfaction
with care are potential benefits of effective communication practices. These are
documented in detail in the iSource National Breast Cancer Centre’s Psychosocial
clinical practice guidelines: providing information, support and counselling for
women with breast cancer.94
Women report a preference for communication styles and patterns that:
• acknowledge the emotional aspects of breast cancer and its treatment
• convey messages in a positive but accurate fashion
• convey friendly interest in the woman as a person
• cultivate a positive attitude7
Positive communication between women and their doctors in an atmosphere of
reassurance is important to allow the assimilation of information and to assist in
women’s psychosocial adjustment.7 In one study, 84 per cent of women reported
difficulty in communicating with the medical team and difficulty comprehending
information.100 Communication problems were strongly positively associated with
mood disturbance.100
Outlined below are a number of general interactional skills to help establish and
maintain effective communication at all stages of treatment.94
General interactional skills

• Express empathy and listen effectively.
• Avoid medical jargon and explain difficult terms.
• Use explicit categorisation.
• Actively encourage questions.
• Actively seek understanding.
• Repeat important information.
• Summarise important information.
• Write down relevant information.
• Tape the consultation as needed and if wanted.
• Send a summary letter as follow-up.
Adapted from iSource National Breast Cancer Centre Psychosocial clinical

practice guidelines: providing information, support and counselling for women with
breast cancer.94
2.2.1 Telling a woman that she has breast cancer

No doctor ever gets used to telling people they have a life-threatening disease,
and nobody has ever developed a formula that will make it easy on either the
doctor or the woman. It requires time, patience, sensitivity and compassion. The
manner in which the diagnosis of cancer is revealed may have important
consequences for the woman’s ability to cope with the diagnosis and treatment
(Level III).101
Telling a woman that she has breast cancer is the responsibility of the senior
clinician involved, and should not be delegated to junior and less experienced
staff. It should not be delayed. Women should be dressed and fully alert when
such discussions are held.102
Non-verbal communication—eye contact, facing the woman, allowing her to
speak without interruption, nodding encouragingly, giving her your full
attention—can be just as important as the actual words spoken when telling a
woman she has breast cancer. If the woman does not understand English well, a
qualified and appropriate interpreter is essential.
Telling a woman she has breast cancer, a recurrence or metastasis
Prior to discussing diagnosis
• Ensure news of a diagnosis is given in person and in a quiet, private place.
• Encourage a second person to be present if appropriate.
• Allow enough uninterrupted time in the initial meeting.
• Arrange to provide other methods to convey the information (eg written
materials, video tapes, tapes of consultations, etc).
Providing information
• Use the general interactional skills suggested on previous page.
• Assess the woman’s understanding of her condition.
• Briefly explain the process by which the diagnosis was reached.
• Provide information simply and honestly.
• Use lay terms, without using euphemisms.
• Avoid the notion that ‘nothing can be done’.
• Adhere to the patient’s preference for information.
• Clearly indicate that the woman will have the final decision regarding her
care.
Emotional and supportive role

• Encourage the woman to express her feelings (eg crying freely, talking about
concerns, fears, anger, anxieties, etc).
• Respond to her feelings with empathy.
• Address disturbing or embarrassing topics directly and with sensitivity.
• Be sensitive to the woman’s feelings and concerns and communicate this
understanding.
• Offer assistance to tell others.
• Provide information about support services.
After discussing a diagnosis

• Summarise the main points of the consultation.
• Assess the woman’s understanding.
• Arrange a further appointment to review the situation within a stated time
period (eg within 24 hours–two weeks).
• Indicate your availability for contact in the interim to address any questions
or concerns.
• Ask if there is anything further the woman would like to discuss.
• Document information given to the woman and family members.
• Let others, particularly the woman’s GP, know the extent of information
given and your perception of her understanding.
Adapted from How to break bad news, by the NSW Cancer Council (1994).102 Source:
NHMRC iSource National Breast Cancer Centre Psychosocial clinical practice guidelines:
providing information, support and counselling for women with breast cancer.94
The words used in discussing the diagnosis and prognosis must be chosen
judiciously. One hundred women newly diagnosed with early breast cancer were
surveyed to determine whether they understood the prognostic information
communicated by clinicians after diagnosis. Many women misunderstood the
language used by doctors to describe prognosis: 73 per cent did not understand
the term ‘median’ survival and 33 per cent believed a cancer specialist could
predict an individual patient’s outcome. The information that women most
wanted was that relating to probability of cure, staging of their cancer, chances of
treatment being successful and 10-year survival figures with and without adjuvant
therapy.103
(Appendix E lists some questions women may ask of their clinicians in relation to
diagnosis, treatment and prognosis.)
2.2.2 Providing information and involving the woman in decision-

making
The attitudes of health care consumers towards their role in decision-making has
changed dramatically in the past three decades, with a trend toward health care
being perceived as a partnership between the health care consumer and the
provider.
A consistent finding is that women want to make a collaborative decision
involving their doctor, family and close friends,104-108 for the following reasons:
• women have little control over breast cancer and many of its treatments
• some women may not entrust treatment decisions entirely to health
professionals109
• the choice between breast conservation and mastectomy is dependent on
clinical imperatives, including the tumour characteristics and breast size,
and on factors that only the woman can assess—personal preference,
lifestyle, the impact on her life of availability of resources and so on.
It is important to discuss with a woman the level at which she wants to be
involved in decision-making.The National Health and Medical Research Council
(NHMRC) says that women are entitled to make their own decisions about
treatments or procedures and should be given adequate information on which to
base those decisions.110 It says:
• information should be provided in a form and manner which helps patients
understand the problem and treatment options available, and which is
appropriate to the patient’s circumstances, personality, expectations, fears,
beliefs, values and cultural background
• doctors should give advice, but should not coerce
• patients should be encouraged to make their own decisions
• patients should be frank and honest in giving information about their
health, and doctors should encourage them to be so110

Explanation of her diagnosis, prognosis and treatment options, accurate clinical
information and information about the likely impact of treatment on the
individual woman’s life should be provided, so that the woman can be fully
informed and encouraged to participate in the selection of surgical and
subsequent treatment.111,112
The information that women may need and request includes:
• the causes of breast cancer
• the extent of the disease
• the proposed approach to investigation and treatment, including
information on expected benefits, the process involved, common side
effects and material risks, whether the intervention is conventional or
experimental, and who will undertake the intervention
• other options for investigation and treatment
• the likely consequences of choosing either another form of treatment, or
no treatment
• the degree of uncertainty involved in all facets of the management
• the time involved
• the costs* involved
• the effect of cancer on interpersonal and sexual relationships
• typical emotional reactions
• any significant long-term effects—including physical, mental, emotional,
social, sexual
• the resources required to adjust to and cope with the disease
• appearance after surgery
• special clothing that may be required
• how to obtain special items, such as wigs and prostheses
• entitlements to benefits and services, such as subsidies for travel or
prostheses
Not all this information need be provided at the first consultation, and
considerable time may be spent in discussion with the surgeon and other
members of the treatment team. Time is needed to reflect on opinions, to ask
more questions and to consult with the family, friends and advisers.110 Some of
the information can be provided in written form—the consumer version of these
guidelines should be provided to women diagnosed with early breast cancer.
State and territory cancer organisations are also good sources of such information
and material.
* (For further information about costs, please refer to JRG Butler & A Howarth. Out-of-pocket expenses
incurred by women for diagnosis and treatment of breast cancer in Australia. NHMRC National
Breast Cancer Centre, 1999).

At diagnosis
Studies have shown that only a little of the initial consultation is remembered. In
one study, women remembered only 25 per cent of the important facts given to
them by their clinician with free recall, and only 33 per cent when prompted.113
It is not necessary to make treatment decisions at the initial consultation.This
gives the woman time to accumulate and digest information which aids in
understanding the disease and treatment options, and to receive support from
family and friends. Waiting a week or two, to seek other opinions, will not have an
adverse effect on outcome.
During the course of treatment

The need for information does not diminish after the initial consultation or after
treatment decisions have been made, but increases during and following
treatment.7 Women with breast cancer and their families will need further
information as they assimilate that given initially. Treatment aims should be
discussed each time the clinical situation changes.
Doctors and other health professionals should be aware of these changing needs,
and give women and their families repeated opportunities to ask questions so
that they don’t feel they are being rushed into a decision regarding treatment.
Doctors frequently underestimate the amount of information their patients want,
and overestimate the amount of time they spend giving information.114 A question
prompt sheet may help115—see Appendix E.
Withholding information
Information should be withheld in limited circumstances only.These are:
• if the doctor judges on reasonable grounds that the woman’s physical or
mental health might be harmed seriously by the information
• if the woman expressly directs the doctor to make the decisions and does
not want the information offered—but even in this case, the doctor should
give the woman basic information about her illness and the proposed
intervention
It is inappropriate for a doctor to withhold relevant information because of a fear
that the woman will be upset by it110 or because the woman’s family requests it.
Assisting women to recall information

When confronted with a diagnosis of cancer couched in technical jargon, many
people do not remember all that was discussed during a consultation. Research
on how to best encourage recall has shown that recall of information increases
when women are provided with: a breast care nurse or counsellor (Level II);116
patient-specific information, such as a tape recording of the consultation
(Level II);117 a follow-up letter (Level II);118 and psychoeducational programs

(Level II).119 Both information recall and psychological wellbeing increases when
the information is tailored to the woman’s particular needs, as opposed to being
given in a standard format (Level I).120 Doctors should consider incorporating
these findings into the consultation.
Women from non–English-speaking backgrounds

If the woman is not fluent in English, a qualified and appropriate interpreter
should be used, rather than a family or staff member. Interpreters are available
free of charge in both the public and private sectors, although they must be
booked in advance of any consultation as their availability is frequently restricted.
Only a qualified and appropriate interpreter can ensure that all the necessary
information passes between doctor and patient. It is important to ensure that the
interpreter is prepared to interpret conversation concerning the woman’s
prospects for survival, and is not restricted from doing so by cultural norms or
constraints.
Written information for women from Greek-, Italian-, Arabic- and Chinese-
speaking backgrounds is available from the iSource National Breast Cancer
Centre.
(Other recommendations about assisting women from non–English-speaking
backgrounds may be found in NHMRC iSource National Breast Cancer Centre
counselling for women with breast cancer).94
2.2.3 Preparing women for specific management, including surgery

In addition to adjusting to the diagnosis of breast cancer, women will undergo a
number of invasive treatments for the disease.
Providing women with emotional support and information about the procedure
that they are about to undergo and what they might expect to feel or experience
reduces their emotional distress and improves their psychological and physical
recovery (Level I).121,122 (The consumer version of these guidelines may assist in
this process.)

Guidelines Level of Reference
evidence
Providing women with support and detailed information I 120–122

about their diagnosis and treatment increases their
emotional wellbeing and assists their physical and
emotional recovery.
Strategies to improve recall of information are II 116–119
recommended, including:
• the provision of a breast care nurse or counsellor
• tape recording of the consultation
• follow-up letter
• psycho-educational programs
2 . 3 C O U N S E L L I N G A N D S U P P O RT
Most women adjust better to having breast cancer if they have good emotional
support from family and friends.89,90
Appropriate counselling for women with breast cancer has been found to
improve emotional wellbeing and quality of life (Level I).120 The term
‘counselling’ refers generically to a form of supportive care delivered by all health
professionals.There are differing levels of sophistication depending on the
training and experience of the practitioner involved.Techniques encompassed by
the term ‘psychological therapies’ and ‘counselling’ are varied and may include
supportive listening, the provision of practical information and education,
instruction in relaxation therapies, assistance with communication and
relationship problems, training in assertiveness and advice on problem-solving.
The selection of a particular therapy depends on the particular needs of the
woman and her social context and the training and experience of the therapist.
Central components of all psychological therapies are an empathic manner, non-
judgemental listening, acknowledgment of concerns, reassurance and emotional
support (see NHMRC iSource National Breast Cancer Centre Psychosocial
clinical practice guidelines: providing information, support and counselling to
women with breast cancer).94
All members of the treatment team play a role in providing support and
opportunities for women to disclose their concerns, feelings and fears. Women
particularly value support provided by the doctors involved in their immediate
care.

A number of trials have assessed the contribution of a breast care nurse and have
shown that such nurses enhance the early recognition of support needs, decrease
psychological distress, and improve continuity of care and understanding of the
disease and its treatment (Level II).79,116,123 Breast care nurses can provide
emotional support, recognise unmet needs, provide information about the
patient’s physical state and treatment and offer practical advice on available
resources.
Support from sources such as family, friends and women who have or have had
breast cancer (including the Breast Cancer Support Service) can be helpful.
Accepting support from family members can be difficult because of some
women’s needs to conceal their own anxiety in order to protect the emotional
wellbeing of those close to them (Level III).104 It is important for doctors not to
presume the nature of the woman’s relationships and to respect her choice of
support person.
While most women will want to see the doctor alone or with a family member or
friend, some women may wish to have the counsellor or breast care nurse
present during the consultation when the diagnosis is given. This will:
• recognise the importance of counselling in patient management
• allow the support process to begin immediately and establish a caring
environment for the woman
• help the counsellor understand what has been discussed
• reduce the possibility of confusion because of conflicting information
• allow the woman to recognise the support from the doctor and the
counsellor together (through the team approach)
Support needs for women with breast cancer and their families may include:
• counselling
• access to a support group or the Breast Cancer Support Service
• assistance with the care of children, elderly parents or an elderly spouse or
partner
• assistance with transport
• the fitting of a prosthesis
• help with accommodation near the treatment centre
Different forms of counselling and support may be needed, depending upon the
specific concern. Women whose primary concerns are associated with self-
esteem, anxiety, body image and sexuality could benefit by personal counselling
and psychological or psychiatric assessment and care. Women whose concerns
relate mainly to treatment and the changes in their lives could benefit from short-
term crisis counselling, the provision of information, advocacy and practical
support.7 A recent Australian study of women with early breast cancer found that
at the time of evaluation 45 per cent of women had a psychiatric disorder, most
commonly depression or anxiety or both. It is possible that this study reported

high figures because women who were more likely to be depressed agreed to
enter the study and agreed to participate in a trial of group therapy. However, it
should be considered whether traditionally used self-report measures are less
sensitive than a structured interview in diagnosing depression in women with
breast cancer, and this may also account for the high figure (Level III).81
Each state and territory operates a Breast Cancer Support Service made up of
well trained volunteers who provide support on a one-to-one basis and who have
the advantage of talking from personal experience. Many women find support
groups and talking to women who have or have had breast cancer useful sources
of information and support.109,124-126 Contact can be made through the local state
or territory cancer organisation.
Depression
For most women the diagnosis of breast cancer represents a major blow. Although
the majority of women will adjust to the diagnosis and treatment, a significant
proportion will develop a depressive illness which requires treatment. The
diagnosis of a major depressive episode in a patient with cancer is best evaluated
by the severity of depressed mood, loss of interest and pleasure, the degree of
feelings of hopelessness, guilt and worthlessness and the presence of suicidal
thoughts.
Estimates of the proportion of women with breast cancer suffering from
depression vary.This may relate to the assessment methods used and the
particular group of women studied, including the stage of their disease. At three
months post diagnosis, it has been estimated that 10–17 per cent of women meet
criteria for a diagnosis of major depression. Other studies at 12–24 months post
diagnosis have estimated rates of depression between 5 per cent and 20 per
cent.79,80,127
The diagnosis of recurrent disease is considered by many cancer patients to be
more distressing than the original diagnosis of cancer. Rates of depression of up
to 42 per cent of patients have been reported among women who have been
diagnosed as having a recurrence.128,129
A retrospective study of 57 patients with breast cancer showed a concordance of
psychiatric diagnosis between the oncologist and the psychiatrist in only 23 per
cent, with the oncologist failing to diagnose a major depression in a significant
number of women.130 Psychiatric morbidity may not always be recognised,
particularly within the stressful context of diagnosis. Clinicians should, therefore,
be alert for signs of depression or emotional distress in women diagnosed with
breast cancer. When appropriate, referral should be considered to a psychiatric
liaison clinic, counsellor, clinical psychologist or to a psychiatrist for treatment,
including medication. Women with suicidal thoughts require immediate referral
to a psychiatrist.

Women should be assured that depression is common in women with breast
cancer, that it is not a sign of personal weakness and that treatments are usually
highly effective. A more detailed discussion of depression in women with breast
cancer can be found in the NHMRC iSource National Breast Cancer Centre
counselling for women with breast cancer.94

evidence
Counselling is recommended for women with breast I 120

cancer, as it improves quality of life.
The involvement of a breast care nurse in the treatment II 79, 116, 123
team is recommended, as this reduces psychological
morbidity.
2.4 CHOOSING A SPECIALIST
General practitioners (GPs) frequently play a key role in recommending the

specialist surgeon or clinical team. Eighty per cent of patients with early breast
cancer were referred to surgeons by a GP and 13 per cent by a screening clinic.131
When choosing a specialist, women and GPs should consider the following
factors:
• the clinician’s experience in dealing with breast cancer
• access to multidisciplinary care
• location (local versus regional centre, especially for rural patients)
• decision-making style (collaborative versus directive)
• possible commitment to clinical research
• variations in cost
There is still considerable variation in the way specialists within a field manage
breast cancer.132,133 In general it is beneficial for a woman to see a specialist who
works with a multidisciplinary team; the evidence shows that the survival of
women with breast cancer is better if they are treated by a specialist who also
treats a large number of similar patients and who has access to a full range of
treatment options in a multidisciplinary setting (Level III).134 An Australian study
has also shown that a rural setting was no impediment to breast conservation or
to a multidisciplinary approach.135
To help GPs provide the most appropriate referrals for their patients, breast
surgeons, medical oncologists and radiation oncologists should be willing to

provide GPs with current information about their practices.This information
could include:
• current management protocols
• use of patient support services
• accreditation status
• approximate fees and charges
• waiting times
• participation in quality assurance programs, including clinical trials,
attendance at conferences and clinicopathological meetings
The provision of such information—perhaps annually through a personal
newsletter—could be an important means of professional education and make for
better communications about referral. Some of this information will be provided
through the continuing education and re-certification requirements of the
professional colleges.
In addition, the GP can bring his or her experience to bear. Previous patients may
have reported their satisfaction or otherwise with particular specialists as regards
the level of communication, their degree of involvement in the decision-making
process, the treatment, the willingness of the specialist to deal with problems,
and the availability of help after hours and on weekends.
The responsibility of the GP in the ongoing care of the whole patient is helped
by the receipt of timely and comprehensive letters from specialists with adequate
information about the management plan, including copies of pathology reports
and other relevant investigations.
The referral letter from the GP should contain all the necessary information to
aid in prompt and appropriate management by the specialist.Test results, films
and other relevant data from the medical record should be forwarded with the
referral letter.
The referral should also help establish good ongoing communication between
the GP and the specialist. GPs require prompt, clear information in writing about
management decisions, follow-up plans and patient progress.
Key point
When organising referral for women with breast cancer, GPs
should consider both the preferences of the patient and the
fact that patient outcomes are better if treated by clinicians
who are part of a multidisciplinary team.

2.5 SECOND OPINION
Women have the right to obtain a second opinion at any time. This can help clear
up any questions in their mind and help them decide which doctor they would
prefer to manage their condition and which course of treatment to follow. It can
also reinforce the accuracy of the advice given by their first doctor of contact.
Should any woman wish to obtain a second opinion, doctors should cooperate
fully in providing all necessary information to the other doctor. This will save time
and the unnecessary repetition of investigations.
Ideally the referral letter should come from the woman’s usual doctor.
2.6 DISCLOSURE OF RISK
Doctors have a responsibility to give information about the risks of any treatment,
especially those that may influence the woman’s decision. Known risks should be
disclosed when an adverse outcome is common even though the detriment is
slight, or when an adverse outcome is severe even though the occurrence is rare.
The Bolam principle—usually summarised as the idea that a doctor is not
negligent if he or she acts in accordance with the behaviour of a reasonable body
of his or her peers—has not been upheld by Australian judges in superior courts
in recent decisions.
Key point
The level of information required to be disclosed changed with
the High Court decision in Rogers v Whitaker (1992).97 The High
Court said:
The law should recognise that a doctor has a duty to warn
a patient of a material risk inherent in the proposed
treatment; a risk is material if, in the circumstances of the
particular case, a reasonable person in the patient’s
position, if warned of the risk, would be likely to attach
significance to it or if the medical practitioner is or should
be reasonably aware that the particular patient, if warned
of the risk, would be likely to attach significance to it.
The NHMRC advises all involved in health care to take note of the spirit of the
law, as well as the letter of the law. Women should be provided with as much
information as they desire, and in a form that is appropriate to their education
and culture. Only then can they make an informed decision regarding treatment.
2.7 CLINICAL TRIALS
Clinical trials are an essential component of the process of finding better

treatments for breast cancer. Each of the three major advances that have been
made to improve the outcome for women with breast cancer has only been
demonstrated to be of clear value because it was first tested in well-conducted
clinical trials.These major advances are:
• the demonstration that the addition of chemotherapy and hormone therapy
to surgery improves survival
• the demonstration that breast conservation is a safe alternative to
mastectomy in terms of survival
• the demonstration that the early detection of breast cancer by
mammographic screening can lead to an overall reduction in the morbidity
and mortality from breast cancer
In Australia, clinical trials are conducted on a large scale through national and
international collaboration (such as the Australian New Zealand Breast Cancer
Trials Group—ANZBCTG). Those trials encompass prevention, DCIS and most
types of early and advanced breast cancer. Other trials in various institutions
address specific questions. (For more information on the different types of
clinical trials and a contact number for the ANZBCTG, see Appendix G.)
The national trials are planned on the basis of available laboratory and clinical
research and are designed to:
• define optimum treatment programs
• test modifications to these programs that might improve outcome
In Australia clinical trials must be approved by an Institutional Ethics Committee
(which might be known as an Institutional Review Board or a Research and
Ethics Committee). Women must be provided with relevant and complete
information about the trial protocol and provide their written consent before
they take part. Entry into a trial must be entirely voluntary, and neither a refusal
to enter a trial nor a decision to withdraw later without giving a reason must
affect the woman’s relationship with her treating practitioner.
Doctors should encourage women with breast cancer to consider participating in
appropriate clinical trials for which they are eligible, as there is indirect evidence
that women who participate in clinical trials have better outcomes than similar
women given similar treatment outside trials.136-138 A high participation rate will
enable outstanding research questions to be answered more quickly.

Guideline Level of Reference
evidence
There is indirect evidence that women who participate III 136–138

in clinical trials have better outcomes than similar
women given similar treatment outside trials.
Women’s concerns about participation in clinical trials include that:139

• the process of seeking participation compromises the role of the doctor in
providing support and information appropriate to the particular woman
• they are being asked to make difficult choices at a time when they are
physically and emotionally vulnerable
• the invitation to participate may be offered in an environment in which
their capacity to give informed consent is compromised
• they won’t know to which group they have been randomised
• they won’t understand the research terms
In discussions about clinical trials, doctors should:
• reassure women that specialists participating in clinical trials are in touch
with the best and most up-to-date treatments available, and are seeking to
improve them
• take time to provide as much information as the woman needs and desires
in a manner in which she can understand so she can make an informed
decision
• explain that the control group in a randomised clinical trial is not a ‘no
treatment’ group and does receive the therapy which would be offered
outside a clinical trial
• not ask the woman to take part while she is in a vulnerable position, such
as undressed or lying down
• not coerce
• allow time for the woman to decide
• inform the woman that she can withdraw from the trial at any time without
prejudice

Key point
All clinical trials must be approved in advance by the ethics
committee of each institution involved. These ethics
committees have been established under guidelines developed
by the NHMRC. They must include men and women from
different age groups, and must include at least one of each of
the following:
• a laywoman not associated with the institution
• a layman not associated with the institution
• a minister of religion
• a lawyer
• a medical graduate with research experience
2.8 PREGNANCY
Pregnancy needs to be considered in several different contexts. There is the

treatment of cancer in pre-menopausal women who have the potential to
become pregnant; there is the treatment of women who are pregnant when
diagnosed; and there is the desire by some women to become pregnant after
treatment is completed.
Prior to the commencement of treatment, women who have not yet had children
may wish to consult with an obstetrician to consider their future options for
fertility. For the woman and her partner to make a realistic decision about
pregnancies, it is important for them to be given information about the most
likely disease course, and risk of recurrence.
Treatment of women who may become pregnant

Although surgery can proceed, even in pregnancy, pre-menopausal women should
be advised to avoid becoming pregnant while being treated with radiotherapy
and chemotherapy or tamoxifen, as the treatment may not be tolerated and may
be damaging to the foetus.
The woman may develop amenorrhoea, which may be temporary in women
under 40 years of age.
Women will vary in the importance they place on fertility and having further
children. Although these are sensitive issues it is important for women to feel that
they can discuss concerns with their clinician. The limited evidence that is
available about pregnancy after breast cancer treatment is presented below.
Treatment of pregnant women
Some studies of women who were pregnant at the time of diagnosis have shown
these women to have lower rates of survival,140-142 while others have not. 143,144
The reasons for this poorer survival, if it exists, are unknown, but it is thought
that the hormonal and immunological changes associated with concurrent or
recent pregnancy may have an impact.145
Surgery can be performed with minimal risk to the baby. The best time to operate
is during the second trimester, although the increased risk of miscarriage from
anaesthetics in the first trimester is fairly small.
Chemotherapy during the first trimester probably increases the risk of congenital
malformations, but during the second and third trimesters this risk is probably
small.
Radiotherapy should be avoided in pregnancy because of the risks to the foetus,
including malignancy in childhood.
Because of the potential difficulties, the treatment of pregnant women should
involve a multidisciplinary team including a surgeon, a radiation oncologist, a
medical oncologist, an obstetrician and a family GP.
Pregnancy after treatment

The potential loss of fertility may be a source of distress for women and their
partners. The decision to have further children after treatment for breast cancer
and the optimal timing of such pregnancies are personal choices.The evidence
from recent studies fails to show that women who become pregnant after
treatment for breast cancer affect their risk of recurrence.146-153
The long-term potential teratogenic effects of chemotherapy and radiotherapy
are not known, but are thought to be minimal.
Women who have had breast irradiation will almost certainly not be able to
breastfeed on the irradiated side.
One study shows that women who have children after treatment for breast
cancer do not suffer increased parental stress, and that for many of these women
having children enhances their quality of life.154
2 . 9 C O M P L E M E N TA RY A N D A LT E R N AT I V E T H E R A P I E S
Most alternative or complementary therapies have not been tested in randomised

clinical trials and proven to be effective. These therapies may involve some
interference with conventional therapies and may cause harm.

However, many people with cancer turn to complementary and alternative
therapies. Nearly 22 per cent of people attending one of three NSW oncology
clinics were using these therapies.155 Other studies overseas and in Australia have
found that 9–54 per cent of adults with cancer 156-160 and 46 per cent of children
with cancer161 use complementary therapies. Most who do so use them as an
adjunct to scientific medicine, while some do so instead of using scientific
medicine. Some people use complementary and alternative therapies to create a
feeling of control over the treatment of their disease, and decisions to use such
therapies might not be based on the same philosophical approach as that used by
doctors.
The main reasons for using complementary and alternative therapies given in the
Begbie et al. study155 were:
• new source of hope (49% of users of alternative therapies)
• preference for natural therapy (40%)
• impression that it is a non-toxic therapy (37%)
• supportive alternative practitioner (29%)
• try something different (23%)
• greater personal involvement (14%)
The main therapies used were:
• relaxation/meditation (59% of users of alternative therapies)
• diet therapy (57%)
• megavitamins (43%)
• positive imagery (44%)
• faith/spiritual healing (30%)
• naturopathy (27%)
• immune therapy (17%)
• homoeopathy (16%)
• acupuncture (11%)
Some therapies such as meditation, relaxation and a healthy lifestyle can work
alongside conventional therapies. Randomised controlled trials of relaxation and
meditation have shown these therapies to be of benefit to patients.162 Relaxation
therapy is commonly utilised by psychiatrists and psychologists and is sometimes
used by GPs and palliative care teams.
Discussing complementary and alternative therapies

Doctors should be aware of any complementary or alternative therapies being
used by their patients and encourage discussion of the use of these therapies in
an open and accepting manner. Women should be advised where the therapy may
be harmful, ineffective or expensive. For example, women should be informed of

the potential interaction between certain unproven therapies (such as high-dose
vitamin C) and some chemotherapy agents.
Patients may, however, perceive that their doctors will be opposed to the use of
alternative or complementary therapies. Forty per cent of women with cancer
who were using such therapies did not tell their doctors.155
Key points
Some complementary or alternative therapies are evidence-
based. However, the majority are not and may interfere with
conventional treatment. Healthy living—including a good diet,
exercise within limits, enough sleep and relaxation, and effective
management of stress—is important for everybody, including
women with breast cancer.
Doctors should encourage discussion of the use of
complementary and alternative therapies in an open manner.
Further information on complementary and alternative therapies and their

effectiveness, safety and costs is available in the section on alternative therapies in
the iSource National Breast Cancer Centre’s Clinical practice guidelines for the
management of advanced breast cancer (2001).162

CHAPTER 3 BEFORE DEFINITIVE
T R E AT M E N T
Optimal therapy for breast cancer is a multidisciplinary activity requiring input

from the woman and the surgeon, the radiation oncologist, the medical
oncologist, the diagnostic radiologist, the pathologist, the general practitioner,
nurses and other health professionals.This may be provided in an integrated
treatment centre or be accomplished elsewhere by consultation between
professionals.
There is reasonable evidence that the survival of patients with breast and other
cancers is better if they are treated by a specialist who also treats a significant
number of similar patients, and who has access to the full range of treatment
options in a multidisciplinary setting (Level III).134,135
The service model favoured by women is one which:
• provides continuity of care
• uses a team approach
• offers psychosocial support
• ensures women’s access to relevant health professionals from one location
• emphasises liaison with community supports such as GPs and community
nurses163
Although surgeons are usually the specialist clinicians of first contact in the
management of a woman with early breast cancer, surgery is only one treatment
modality. Since adjuvant radiotherapy or systemic therapy is also used in many
cases, other specialists should become involved in the planning of definitive
treatment.
Pre-operative consultation with a radiation oncologist should be considered if
radiotherapy is thought to be likely. Because the need for systemic therapy is
usually determined by the histology of the tumour and regional lymph nodes, it is
reasonable to involve a medical oncologist in treatment planning at a later stage.
In certain cases, it is appropriate for the medical oncologist to be involved before
treatment begins.
In all cases the woman will require a varying degree of support, ranging from
practical advice about obtaining a breast prosthesis after mastectomy to
professional counselling when emotional or psychological problems occur.
Clinicians who treat women with breast cancer should inform them how to
access appropriate support services.164
The woman herself has an important role in the planning of treatment for breast
cancer. She should be encouraged to participate in the selection of surgical and
subsequent treatment111,112 and should be informed fully about the appropriate
treatment options.This may involve considerable time in discussion with the

surgeon and other members of the multidisciplinary team, but it is an essential
step in the preparation for definitive treatment.
Australian doctors have a duty of disclosure which involves informing the patient
of any material risks associated with any procedure. A material risk is defined as
any risk which a reasonable person in the patient’s position would regard as
significant and which by implication might influence a decision in the selection
of treatment.97

evidence
The outcome of patients with breast and other cancers III 134
is better if they are treated by a clinician who has
access to the full range of treatment options in a
multidisciplinary setting.
3 . 1 H I S TO RY
A full clinical history can be of great value in the management of women with
breast cancer. Apart from establishing a professional association, the doctor is able
to obtain information about other relevant medical conditions.
Matters such as symptomatology (including pain) and menstrual, obstetric, family
and medication history can be of importance, and such a record gives valuable
information about the woman’s background. In addition, obtaining details of the
woman’s social situation may provide valuable information about her risk of
suffering increased emotional distress, given the known psychosocial risk factors
(refer to section 1.5).
3 . 2 C L I N I C A L E X A M I N AT I O N
A thorough physical examination follows the history, and should precede other
investigations. It should involve examination of both breasts and axillae for signs
of primary cancer and local spread, and a thorough examination of the rest of the
body for signs of distant spread.
A knowledge of the physical findings can be of value in sequencing investigations
and making plans for therapeutic approaches. That knowledge can also assist in
raising awareness of potential difficulties that could be avoided by good planning.
Clinical examination of the breast and of the regional lymph nodes is important
in the assessment of the patient, but clinical examination is not completely
reliable and needs supplementation from other diagnostic modalities. For
example, one small study showed that clinical examination had a sensitivity of
only 37 per cent in women under the age of 35 (Level III).165
The error rate in clinical assessment of axillary lymph node metastases is
between 30 per cent and 50 per cent (Level III).166,167
One study reviewed eight series totalling 2109 women and found that the triple
test of clinical examination, breast imaging and aspiration biopsy provided an
accuracy of 99.1 per cent. Due to the difficulties experienced with
mammography in the dense breasts of young women, they suggested that an
increased use of open biopsy was reasonable in women under 35 years of age.168
3 . 3 I N V E S T I G AT I O N S
The following diagnostic modalities are currently used in the preoperative

assessment of primary breast cancer. Since all are known to have limitations, they
are usually used in combination. Diagnosis is established by:
• history and clinical examination
• breast imaging: mammography with/without ultrasound
• fine needle aspiration biopsy or core biopsy
Clear, accurate clinical information in the referral will assist the radiologist in
providing the most appropriate targeted imaging.
While most of these tests will be performed so a diagnosis can be made, some
may be used for further refinement between the time of diagnosis and the
commencement of treatment.
Each of these investigations will provide different information, and none used
alone is able to identify all cases of breast cancer.169 It is therefore recommended
that the triple test be used in investigating breast symptoms.This approach is
outlined in The investigation of a new breast symptom: a guide for general
practitioners.170 (Also refer to The pathology reporting of breast cancer. A guide
for pathologists, surgeons and radiologists. 1997, Australian Cancer Network.)
Mammography
In women with clinically detected breast cancer, mammography should be
performed to detect cancer in the contralateral breast. In the affected breast, it
measures the extent of the primary tumour and may demonstrate multifocal
disease.
In women with DCIS or extensive intraductal carcinoma (EIC) associated with an
invasive tumour, mammography may give a more reliable preoperative assessment
of the extent of the disease than clinical examination (Level III).171 But even

mammography is likely to underestimate the extent of the disease process in
women with DCIS (Level III).172
In women with clinically palpable breast cancer, the combined use of clinical
examination and mammography is likely to provide the best available assessment
of the extent of disease in the breast. A good working relationship between the
surgeon and the diagnostic radiologist can assist in decision-making.
Breast ultrasound
Breast ultrasound provides a reliable method for the assessment of tumour size in
most cases of invasive breast cancer, particularly in dense breast parenchyma
where mammography may fail to demonstrate clearly the margins of the tumour
(Level III).173
Ultrasound has also been shown to be useful in the detection of small breast
cancers, particularly in younger women with dense breast tissue which is not
suitable for mammography.174
Some types of breast cancer such as invasive lobular carcinoma may not be
detectable by either mammography or ultrasound examination.
Breast ultrasound is not routinely used for screening.
Key point
Not all cancers can be detected by mammography or
ultrasound. Even if both tests are negative, a persistent lump
should be investigated. Mammography and ultrasound should
never be relied upon exclusively to diagnose any condition in
the breast.
Fine-needle aspiration biopsy

Cytological examination of material obtained by fine needle aspiration has been
used for many years to establish a preoperative diagnosis in cases of palpable
breast cancer.175 In the case of an impalpable lesion, a cytological sample can be
gained by fine needle aspiration guided by either mammography or breast
ultrasound (Level III).176 It may require hook wire localisation and imaging.
The accuracy of breast cytology is very high when carefully performed and the
cytologist is expert.177 When a diagnostic sample of malignant cells is obtained, it
may be possible to proceed directly to definitive surgery without a preliminary
open biopsy.178

Fine-needle aspiration biopsy (FNAB) provides a cytological rather than
histological diagnosis. Before definitive surgery, it is necessary to have clinical and
imaging support for the cytological diagnosis.
Hormone receptor status can be determined using cytological aspirates.
Core biopsy
Core biopsy uses a wide bore needle to obtain a tissue sample which may
provide a definitive histological diagnosis. As for fine needle aspiration, core
biopsy may be performed on palpable lesions or, with mammographic or
ultrasound guidance, on impalpable tumours (Level III).179 Where calcification is
present, it should be submitted for a specimen X-ray to ensure correct sampling
of the lesion.
Core biopsies need to be done by those familiar with the technique and its
application in patient care. If the lesion is palpable, core tracks should be placed
in such a way as to enable surgical excision of the track. This is also preferable for
stereotactic core biopsies of impalpable lesions, but not always possible. In this
situation, prior planning should be conducted in conjunction with the treating
surgeon or multidisciplinary team.
Key point
The use of either fine needle aspiration or core biopsy to
establish a preoperative diagnosis allows detailed discussion
with the woman about surgical management and may permit a
one-stage surgical procedure.
(See iSource National Breast Cancer Centre guidelines on Breast fine needle
aspiration and core biopsy, in preparation.)
Open biopsy
When a cytological or histological diagnosis has not been obtained prior to
surgery and there is still a strong clinical suspicion of malignancy, an open biopsy
can be used to obtain a tissue diagnosis. It can be done either as an independent
procedure or as part of a planned treatment procedure.
It is preferable to obtain an open biopsy as an independent procedure. This
provides detailed information about the type and extent of the tumour, together
with material for the assessment of hormone receptor proteins and other
prognostic indices, before treatment is discussed. Information about the extent of
disease, including vascular or lymphatic permeation and the presence of EIC, is of
value in planning further surgical procedures.180,181

Where possible, a small lesion should be excised completely, when open biopsy is
performed.
Impalpable lesions may require needle localisation under mammographic or
ultrasound control before open biopsy to assist surgical location. Excised
specimens should be submitted for a specimen X-ray or ultrasound. They should
be oriented by the surgeon and the tissue must not be incised.
Frozen section histology

Frozen section examinations of breast specimens have a limited role in the
management of the patient with a palpable breast lesion. However, it may be
necessary for confirming the diagnosis of the malignancy at the time of surgery
and prior to definitive treatment, when that diagnosis is strongly suspected on
clinical or radiological grounds but has not been made by preoperative fine
needle or core biopsy. It is not often indicated in the management of women with
clinically impalpable lesions.182
• Frozen sections should not be performed in cases where the pathologist
believes that subsequent examination is likely to be prejudiced.182
• Fine needle or core needle biopsies are now widely available and have been
shown in many studies to be as accurate as frozen sections. Frozen sections
are not recommended for needle localised excision biopsies unless
preoperative diagnosis has not been made and the lesion is easily palpable
within the resected specimen.182
• While cytological analysis of malignancy may typically be conducted before
definitive surgery, frozen section may be used intraoperatively to confirm
histologically a preoperative cytological diagnosis. It may be used to obtain
an immediate diagnostic report when an open biopsy is performed as an
independent procedure. It should not be done unless the surgeon can
preserve the integrity of the specimen so as not to compromise tumour
margins or subsequent histology.
• When a preoperative diagnosis has not been obtained, the use of frozen
section histology to determine immediate definitive treatment, such as
mastectomy, does not allow adequate discussion with the woman about her
surgical management. Such a policy should be rarely used. An exception to
this is when other investigations have strongly indicated the presence of
cancer, and the woman has expressed a preference to undergo definitive
treatment as a one-stage procedure. This may occur when the woman has
expressed a preference to proceed directly to axillary dissection if a breast
conservation procedure is indicated. It may also occur when mastectomy is
the treatment of choice based on clinical and radiological findings, but only
if the woman is prepared to proceed with this management without
further discussion.

While some women are prepared to give consent for defined surgery to proceed
depending on intraoperative findings such as frozen section, most women would
feel uncomfortable about making the decision for a possible mastectomy in this
way.
Other pre-operative investigations

Apart from mammography, the selection of other investigations should be
determined by the doctors involved in the patient’s care.
Full blood count and serum biochemistry may give useful information in selected
cases, but imaging investigations—including chest X-ray, bone scan, liver
ultrasound and chest computed tomography (CT)—have a low diagnostic yield.183
They should be used only when clinically indicated. Such indications include:
• symptoms of lung disease
• a palpable liver
• abnormal liver function tests
• bone pain
• bony tenderness
Serological tests for cancer-specific antigens, such as CEA and CA 15.3, are non-
specific and unreliable as indices of active disease.183
Key point
All diagnostic modalities have an error rate and it is advisable
to use more than one modality to obtain a preoperative
diagnosis. The combination of clinical examination,
mammography, ultrasound and fine needle aspiration cytology
provides the highest diagnostic accuracy and the lowest risk of
diagnostic error, particularly in women over 35 years. An
increased use of open biopsy is reasonable for suspicious or
indeterminant lesions where a definite benign needle biopsy has
not been obtained in women less than 35 years of age.
3 . 4 P AT H O L O G Y
Pathological examination of the specimen is an essential part of the management

of breast cancer.The examination and reporting of breast specimens should be
undertaken in line with the Australian Cancer Network’s guidelines for The
pathology reporting of breast cancer.182 (This document is currently being
updated.)
Pathological examination has three main aims:
• to provide a diagnosis
• to confirm the complete removal of the lesion
• to provide extra information useful for management, such as tumour
markers and oestrogen receptors
Re-excision should be performed if pathological examination shows the margins
were involved.
Pathological examination is easier if diathermy is not used on the specimen.The
excised specimen should be oriented by the surgeon at the time of excision.
Synoptic pathology reports should contain, as a minimum, the following
information:
• tumour size
• type
• histological grade
• tumour margins
• presence or absence of multifocality
• the presence or absence of DCIS, both within the tumour and around it
• the presence or absence of vessel space invasion in the main tumour
• number of axillary nodes identified and examined182,184
• extracapsular spread
• oestrogen receptor status
• progesterone receptor status
It is recommended that receptor analysis be routinely requested and obtained.
Present evidence indicates that hormone receptor status from
immunohistochemistry testing is reliable and can be extended to cytological
aspirates.
For further information on pathological testing and reporting, refer to The
pathology reporting of breast cancer.182
To assist the pathologist, surgeons should send all excised lymph nodes for
examination. Clinicians should specifically request hormone receptor status on
the pathology form. If it is not requested, the hormone status will not be readily
available for decision-making, and the woman will not be reimbursed for the test
if it is done.
Note that oestrogen receptor status can be determined on cytological aspirates,
freshly excised specimens and paraffin block specimens.

Other information—such as degree of angiogenesis, proliferative rate, cathepsin D
expression, epidermal growth factor receptor expressions, pS2 expression and
the presence of heat shock/stress proteins—can be obtained by special staining,
but much of the data are yet to be proved clinically useful.
Key point
It is recommended that receptor analysis be routinely
requested and obtained.

CHAPTER 4 S U R G E RY F O R I N VA S I V E
BREAST CANCER
The aim of surgery for primary breast cancer is to eradicate the primary tumour
and any local extension in the hope of achieving total disease control.
Indirect evidence suggests that surgical intervention may extend survival from
the time of clinical detection. In an historical comparison, women treated by
radical mastectomy appeared to survive longer than women whose breast cancer
was untreated,185 and in the long-term follow-up of women treated by radical
mastectomy, about 30 per cent of women were alive 30 years after surgical
treatment (Level III).186
There have been two randomised trials involving women over 70 not having
surgery. In the first, women were randomised to either tamoxifen 40mg daily or
tamoxifen plus optimal surgery.187 At a median follow-up of 34 months, many
women on tamoxifen alone had progressed to surgery, but there was no
demonstrable difference in quality of life or survival rate.The trial is continuing.
However, a number of women over the age of 70 years are of good performance
status and good prognosis and should probably be treated along standard
treatment lines, which in most circumstances would be wide local excision
followed by post-operative radiotherapy. There is no evidence to suggest that
these patients have any greater difficulty coping with such treatment.
In the second trial,188 women were randomised to either wedge resection or
tamoxifen 40mg daily. At a mean follow-up of 65 months, significantly more
women in the tamoxifen group had progression of their cancer.There was no
difference in overall survival, cause of death, the rate of metastases or the site of
initial metastasis.
Further evidence supporting the value of surgical excision is provided by
randomised controlled trials of screening mammography. Women offered
mammographic screening and treatment of screen detected cancers have
significantly lower mortality than women in unscreened control groups in
population-based trials of mammographic screening (Level I).189
The surgical treatment of primary breast cancer has devolved into two basic
procedures:
• complete local excision (CLE) with axillary dissection
• total mastectomy with axillary dissection
4 . 1 B R E A S T C O N S E RV I N G S U R G E RY
Breast conserving surgery demands CLE, which by definition means clear
histological margins with a rim of normal breast tissue around the periphery of
the primary tumour on all sides. This procedure is suitable for tumours which are
unifocal and in which clear margins can be obtained, if necessary by including
overlying skin. All the requirements of treatment must be taken into account
when planning the incision.
There is no absolute limit to the size of a tumour which can be locally excised
without incurring a high risk of recurrence; 3–4cm is often regarded as a
practical limit.190 The aim of treatment is to maximise control of the disease and
decrease the impact of breast cancer on the woman’s quality of life. However, the
relativity of tumour size to breast size and the achievement of an acceptable
cosmetic result are equally important considerations.
A breast conserving protocol comprises CLE in which clear margins are obtained
by any surgical technique (including segmentectomy and quadrantectomy),182
combined with axillary dissection and followed by adjuvant radiation therapy to
the breast (see below). Completeness of excision minimises the risk of local
recurrence. There are no reliable data to show a definite width of margin that is
necessary for complete excision, but re-excision should be considered where the
tumour extends to and or involves the margin.
For specimens of impalpable lesions that are accompanied by a specimen
radiograph, it is essential to correlate the radiological and histological
appearances. Blocks should be selected from the area of the radiological
abnormality which can be identified, by either slicing or repeating an X-ray of the
slices or by using a localisation device in which a grid reference is used to locate
the areas of interest. Either method is acceptable. Any lesion present within the
specimen should be described and its maximum dimension recorded in
millimetres. The relationship of the lesion to the excision margins should be
recorded and the distance to the nearest margin or margins, measured.182
Very small, well differentiated tumours are associated with decreased levels of
axillary involvement, and in such cases after discussion, consideration may be
given to omission of axillary dissection. It should be noted that even in T1b
tumours (6–10mm), the probability of lymph node involvement approaches
20 per cent (Level III).191 Studies of sentinel node biopsy may help to resolve this
issue (see also section 4.4, Management of the axilla). (see Appendix C for TNM
clinical classification).
When the omission of axillary dissection from a breast preserving protocol is
considered, the woman should be fully informed of the risk of axillary node
metastases being undetected. Radiotherapy could be offered as an alternative.
4 . 2 T OTA L M A S T E C TO M Y
In clinical trials conducted in the 1960s, total mastectomy combined with axillary
dissection or radiation treatment to the axilla achieved survival rates similar to
those achieved by the Halsted radical mastectomy.192 Later studies confirmed this
(Level II)193,194 and there is now essentially no role for Halsted therapy in modern
care of breast cancer.195
The surgical protocol for a total mastectomy includes complete excision of the
breast parenchyma with preservation of the underlying pectoral muscles.
Total mastectomy is an appropriate treatment for women whose tumours extend
widely within the breast, have ill defined margins which defy CLE, directly
involve the nipple or overlying skin, or who do not choose breast conservation.
Nipple involvement does not always preclude breast conservation. In such cases,
excision of the central breast tissue, including the nipple, is often feasible. It is
reasonable to reconstruct the nipple as a secondary procedure.196
Skin sparing and nipple preserving mastectomy with immediate reconstruction
may have a place in the treatment of early breast cancer. Although no long-term
results of this technique are yet available, early data suggest no increase in the
risk of local recurrence when tumours of comparable size are treated by skin
sparing mastectomy as opposed to total mastectomy (Level III).197-199
4 . 3 C O M PA R I S O N O F B R E A S T C O N S E RV I N G S U R G E RY
W I T H M A S T E C TO M Y
Pre-operatively, about 70 per cent of mammographically detected cancers and

50 per cent of clinically detected cancers appear suitable for breast
conservation,200 and this option should be discussed with the woman.
Numerous randomised, controlled clinical trials have demonstrated no difference
in distant metastases or survival among women with operable breast cancer
treated by mastectomy compared with those treated by breast conserving
surgery (Level I),195,201-203 when both have included axillary dissection.
The incidence of local recurrence is 1–2 per cent per year in women who have
breast conserving surgery followed by radiotherapy.204 In comparable tumours,
the incidence of local recurrence following mastectomy is 3–5 per cent at 10
years, or less than 0.5 per cent per year.205
The choice of surgery is an individual one and each woman should be fully
informed of her options, including the risks and benefits of each procedure. The
woman should be informed that local recurrence can occur even in surgery
properly performed and she should be made aware of the potential need for
further surgery if the margins are positive.
The cosmetic result of breast conserving surgery has a high level of
acceptance,206 gives an opportunity to preserve the breast shape, avoids the need
for a prosthesis or reconstructive surgery, facilitates a better fit of clothing and in
general is associated with less impact on body image and sexuality.These are
factors which may influence a woman’s decision in favour of breast conserving
surgery. In discussion of choice between breast conserving surgery and
mastectomy, women should be informed that body image is better preserved
with conservation surgery (Level I).207

evidence
In discussion of the choice between breast conserving I 207

surgery and mastectomy, women should be informed
that body image is better preserved with conservation
surgery.
Specific situations in which mastectomy may be preferred to breast conserving

surgery include:
• a tumour of such a size relative to the breast that a satisfactory cosmetic
result may not be obtained
• multifocal disease
• co-existence of extensive intraductal carcinoma or DCIS which is of high
grade and which cannot be excised with clear margins
• prior radiation therapy to the breast
• previous history of collagen disease, particularly scleroderma
• widespread indeterminate micro-calcification within the breast, which may
make mammographic follow-up difficult
• when the woman chooses mastectomy in the knowledge that the two
treatments are equally effective
Studies comparing breast conserving surgery and mastectomy have shown similar
psychosocial morbidity for both procedures, even twelve months after surgery
(Level III).80 However, an influential factor during the first twelve months
appears to be choice, with those offered a choice of surgery experiencing fewer
psychological difficulties in the first 12 months than those who were not
(Level III);80 this was not evident three years after surgery.208
Regardless of surgery type, some women will suffer problems with sexuality,129,209
although there is some evidence that this effect is less marked in women having
breast conserving therapy.129 The most consistent finding is that body image is
much better in women who have breast conserving surgery.73,129,207 Further
research is needed to elucidate the impact of different forms of surgery on
physical health, anxiety, depression and global quality of life.
Overall, there is no evidence for a substantial difference in post-operative
psychological health between women who have had breast conservation and
those who have had mastectomy,80,210-215 although the focus of anxiety may be
different.
Many women who have mastectomy will be able to have breast reconstruction.
In some cases, this can be planned before mastectomy and carried out at the
same time. Women with cancers suitable for immediate reconstruction should be
informed of this option before surgery.
evidence
Where appropriate, women should be offered a choice I 195

of either breast conserving surgery followed by
radiotherapy or mastectomy, as there is no difference
in the rate of survival or distant metastasis.
4 . 4 M A N AG E M E N T O F T H E A X I L L A
Management of the axilla has several aims:

• eradication of metastatic disease within the axillary nodes
• assessment of nodal status for evaluation of prognosis
• assessment of nodal status to determine adjuvant therapy
Both dissection and irradiation are used in managing the axilla. The best approach
needs to be considered, as there are side effects from both axillary dissection and
axillary irradiation—in particular, lymphoedema. Reported estimates of rates of
lymphoedema following axillary surgery (sampling or dissection) and/or axillary
irradiation vary widely, reflecting the methodological weaknesses of many of the
studies that have investigated the prevalence of lymphoedema following
treatment for breast cancer.216 Rates of between 0 per cent and 58 per cent for
axillary dissection alone (six studies); between 0 per cent and 11 per cent for
axillary sampling (two studies) and 8 per cent for women who received axillary
irradiation alone (one study) have been reported.216 When both axillary surgery
(dissection or sampling) and irradiation are given, reported rates of lymphoedema
range between 6 per cent and 60 per cent (nine studies).216 However, analysis of
the significance of much of this research is complicated by the lack of
comparability between studies and measurement methods, small sample sizes,
poor differentiation of subgroups and methodological problems in individual
studies.216
Axillary dissection
The extent of axillary dissection can be defined with reference to the pectoralis
minor muscle:
• level 1: lower axilla up to the lower border of pectoralis minor
• level 2: axillary contents up to the upper border of pectoralis minor
• level 3: axillary contents extending to the apex of the axilla
All nodes removed should be sent to the pathologist for examination.

Survival
The benefits of axillary dissection in prolonging survival are unclear; studies have
reported different effects on survival and most have some methodological flaws.
For example, the NSABP 04 trial205 found that there was no difference in survival
between women who had simple mastectomy and those who had radical
mastectomy (including axillary dissection). However, 33 per cent of women in
the non-dissected group had undergone some form of limited axillary surgery and
the power of the study may have been insufficient to demonstrate a clinically
significant difference between the groups.
Other studies have found overall long-term benefits in survival when axillary
dissection was carried out.192,217,218 For example, Cabanes’ study of lumpectomy
plus breast and axillary irradiation without axillary dissection, versus
lumpectomy plus breast irradiation with axillary dissection, showed a small but
significant improvement in survival in women who had axillary surgery (92.6% vs
96.6%, p=0.014).217 However, interpretation of these results is difficult since a
significant proportion of the axillary dissection group received adjuvant systemic
therapy based on their nodal status.
Prognostic information
Axillary dissection also provides information about nodal status for both
prognosis and the planning of adjuvant treatment.
Axillary lymph node status is the most powerful single variable in the estimation
of prognosis for primary breast cancer. Prognosis is related to the number of
axillary nodes which contain metastases—this relationship applies to both
disease-free interval and to survival.219
As a means of selecting women for adjuvant systemic therapy, the number of
nodes involved is important since the benefits of therapy are expressed as a
reduction in risk. The probability of lymph node involvement is related directly to
the size of the primary tumours. Larger tumours are more likely to have
metastasised to axillary lymph nodes than smaller ones. But even in small primary
tumours (T1a), the risk of nodal metastases approaches 20 per cent.191 In the
presence of nodal involvement adjuvant radiotherapy has been shown to have a
significant influence on disease-free survival, to reduce locoregional recurrence
and, in a few studies, to improve overall survival.220,221 (See section on Axillary
Irradiation below.)
At this time, axillary dissection is the only reliable technique for determining
lymph node status.
Axillary sampling is an ill-defined procedure and is not recommended as an
alternative to axillary dissection. Axillary sampling may imply the removal of a
single lymph node for histological examination, or a dissection of the axillary

contents extending to level 1. Although there is now some evidence from
randomised controlled trials222,223 which shows that this technique produces
qualitative information about whether an axilla is histologically involved under
some circumstances, the accuracy of the procedure has not been validated by
other centres. At this time axillary sampling is considered unreliable in assessing
the presence of axillary lymph node metastases because of the high false negative
rate.224
Sentinel node biopsy

Sentinel node biopsy is being studied,225,226 but is not currently considered an
alternative to axillary node dissection and the procedure should only be
performed as part of a controlled study or as a prelude to dissection. In the future,
after appropriate controlled randomised trials have been completed, sentinel
node biopsy technologies may modify the approach to the axilla.
Axillary irradiation
The selective use of radiotherapy in patients with increased risk of recurrence is
beneficial (Level II).220,227 Two studies220,227 have shown a survival benefit for post
mastectomy radiotherapy that included the axilla (and the internal mammary
chain and supraclavicular fossa), and another trial has shown a trend towards
improved survival.221 However, a large overview failed to demonstrate a survival
benefit for post-operative radiotherapy.195,228
Axillary irradiation following dissection in women with limited nodal

involvement
Relevant data are provided by extrapolation of results from several large
randomised trials201-203 which compared breast conserving therapy and
mastectomy. They suggest that there may be little benefit from adding axillary
irradiation among women who have had axillary dissection and who have only a
small number of involved lymph nodes.
For example, the NSABP-B06 trial202 reported that 90 per cent of patients had less
than four lymph nodes positive in a dissected axilla. Local axillary relapse in this
entire series is low, at around 1–3 per cent. It is unlikely that the addition of
radiotherapy will confer much benefit where rates of relapse are already very low.
This conclusion is supported by a strong body of retrospective data.201,229 Data
from the Mayo Clinic suggest isolated locoregional recurrences (that is,
recurrences on the chest wall or lymphatic areas) of only around 8 per cent of
women with less than four lymph nodes involved.230 Similarly, Fowble et al.231
suggest isolated locoregional recurrences of 7 per cent in this group. Of the 634
patients analysed in this study, only 1.3 per cent recurred in the axilla alone and
another 1.3 per cent in multiple sites that included the axilla—that is, the total
axillary recurrence rate was only 2.6 per cent.231
Fisher232 analysed patterns of recurrence in 320 patients who had been treated
for Stage II or III breast cancer with surgery and chemotherapy without
locoregional radiation therapy. Twenty-one isolated axillary recurrences were
found (6.6 per cent) at a median follow-up of 77 months. The number of axillary
nodes involved was not predictive of recurrence.
Axillary irradiation following dissection in women with greater lymph

node involvement or remaining disease in the axilla
While these data suggest that there is little to be gained by axillary irradiation in
women with only a small number of involved lymph nodes, it seems that there
may be benefit from the addition of radiotherapy when it is likely that there is
remaining disease in the axilla—for example, when the surgeon believes that
macroscopic disease was left behind or transected, or when the pathologist
indicates positive margins.
The addition of axillary irradiation with greater nodal involvement is more
controversial.232-235 When there is greater nodal involvement, local relapse rates
will be increased for surgery alone. For example, data from the Mayo Clinic203
suggest isolated locoregional recurrences at three years of 14 per cent among
women with 4–7 positive nodes and 22 per cent for women with eight or more
positive nodes. Similar data have been reported by Fowble et al.231 However, not
all of these relapses are axillary. Most studies have shown at least 50 per cent to
be on the chest wall. These studies are unrandomised.232-235
The three randomised trials220,221,227 noted above which showed an improvement
in survival in high-risk disease for patients irradiated to the entire lymphatics and
chest wall, showed a reduction in locoregional relapse from 32 per cent to 9 per
cent at ten years. Again, the distribution of local relapses was not given, but more
than half were on the chest wall. Axillary recurrences remain uncommon even in
patients with heavy nodal involvement. Not all analyses have demonstrated
increased axillary relapse rates with increasing numbers of involved nodes.232
It is important, however, to consider the role of axillary irradiation in patients at
high risk of local recurrence. Not all axillary recurrences can be salvaged. It is
particularly difficult to salvage axillary recurrence with radiotherapy where the
axilla has been previously selectively excluded from the chest wall and
supraclavicular fossa volume. The prevention of recurrence is therefore a
preferable option, although it carries the cost of increased risks of lymphoedema.

evidence
For most women with early breast cancer, a level 1 or II 205, 217
level 2 axillary node dissection should be standard.*
* See Table 1 for recommendation summary.

Summary
Treatment of the axilla by either dissection or irradiation will reduce rates of
axillary recurrence. In practice, most women will be offered axillary dissection as
the first choice since this will also provide information to assist in staging and in
contributing to decisions about systemic and locoregional adjuvant treatment.
While data are limited, general agreement was reached on certain
recommendations for the management of the axilla at the Meeting on Axillary
Dissection and Irradiation held at the Gold Coast, Australia in September 1998
(see Table 1 for a summary).
For some women, irradiation rather than dissection will be the preferred method
of axillary control. This includes selected women in whom the result of axillary
dissection would be unlikely to influence the decisions about systemic adjuvant
therapy. Other women may not wish to have further surgery, and any decision
should involve consultation with appropriate members of the multidisciplinary
team.
Some women at high risk of axillary recurrence will require both axillary
dissection and axillary irradiation. In particular, this will include those women
who have remaining axillary disease following dissection.
Table 1: Recommendations for management of the axilla*
• For women with early breast cancer, a level 1 or level 2 axillary node
dissection should be standard.
• The omission of axillary dissection can be considered for some women,
including: selected patients in whom the result of axillary dissection would be
unlikely to influence the decisions about systemic and locoregional adjuvant
therapy; and women with an isolated small low grade carcinoma.
• Axillary irradiation will reduce axillary recurrence.
• Where the risk of axillary recurrence is high, both axillary dissection and
axillary irradiation should be considered. In particular, this will include those
women who have remaining axillary disease following dissection.
• Management of the axilla should be determined by a multidisciplinary team in
discussion with the patient. Patients should be informed of the benefits and
risks of axillary dissection and axillary irradiation.
*Source: Recommendations from the Meeting on Axillary Dissection and Irradiation held at the Gold
Coast, Australia, September 1998.

4.5 BREAST RECONSTRUCTION
After treatment for breast cancer, women may have concerns about their
appearance. For example, in a recent Australian study, 29 per cent of women
reported feeling substantially less attractive and 13 per cent were unable to look
at themselves naked after treatment for breast cancer and had low self-esteem
following a mastectomy.129 The study included women who had had either breast
conserving surgery (54 per cent) or mastectomy (46 per cent), but the data were
not analysed separately.
Breast reconstruction involves the use of a prosthesis or of tissue from other
parts of the body to rebuild a breast removed by mastectomy. It does not interfere
with the treatment of breast cancer.
The decision to choose breast reconstruction is a complex one and opinions vary
as to whether it should be done at the time of treatment or later. Women should
be given the opportunity to consider the procedure, so they can balance the
advantages and disadvantages of reconstruction after mastectomy.236-239
Methods of reconstruction
The actual method of reconstruction will depend on the nature of the problem.240
There is no single method that is suitable for all women.240
In women with small breasts, a prosthesis may be a satisfactory method and may
be used alone, or in association with a tissue expander.This latter device is used
to achieve a gradual increase in the amount of available skin cover. A second
procedure may be required to replace the expander with a definitive prosthesis.
Complications occur in about 10 per cent of patients (Level III).241
In some selected women with large and heavy breasts, a breast sharing
reconstruction may be possible. With this technique, tissue from the other breast
is taken for the reconstruction. Infection and loss of tissue occurs in about 5 per
cent of cases (Level III).242
Skin and fat may also be transferred from the back, using the latissimus dorsi
muscle as a flap. Donor site morbidity is minimal and complications of infection
and tissue loss occur in fewer than 5 per cent of patients. A prosthesis may be
necessary to augment the breast volume, and complications occur in fewer than
5 per cent of patients.243
In women with a suitable amount of loose skin and fat on the abdomen, a transfer
of this tissue, either as a pedicled flap or as a free microvascular transfer, may be
used. This is known as the TRAM (transverse rectus abdominis myocutaneous)
flap method of breast reconstruction. The complications of infection and loss of
tissue occur in about 5 per cent of patients. A further 10 per cent suffer some
weakness and bulging of the abdominal wall.244 Because more muscle in used in

the pedicled technique, the risk of abdominal weakness is potentially greater than
with the microsurgical approach. Other potential complications of either the
microsurgical or pedicled methods of reconstruction include fat necrosis in the
reconstructed breast and asymmetry with the other breast.
There is no evidence that breast reconstruction increases the risk of recurrence
of the original tumour, or that there is any significant impairment of the ability to
detect any recurrence.245 However, continuing follow-up (including
mammography) is advised, as all women who have had a cancer of the breast
have a small but definite increased risk of developing a new cancer in the residual
breast tissue.
Although there is no evidence that the use of silicone prostheses poses any long-
term risk to general health,246 significant numbers of women have local reactions
to the prostheses, which may develop a tight capsule, become hard or be
rejected.246 Because of the controversy surrounding silicone breast implants,
these have been replaced largely by saline-filled implants. Soft tissue
reconstruction is preferred by many women, particularly if there have been
complications from the use of prostheses.
Psychological issues
There is no evidence that women who seek breast reconstruction are, as a group,
psychologically vulnerable.247
No randomised trials of the impact of breast reconstruction on patient wellbeing
have been located. However, it appears that reconstruction may help women
worry less about their health, as the surgery helps repair the constant reminder
of the life threatening nature of the disease.248 Psychological health may be
improved in the short term and body image may be improved at three and twelve
months.249
Women who have breast reconstruction are almost always happy with their
decision.They report a number of benefits, including: a feeling of being whole
again, better psychological and social adjustment to their cancer and mastectomy,
more positive body image, better sexual adjustment, less depression and feeling
more comfortable without a prosthesis.237
4 . 6 E X T E R N A L B R E A S T P RO S T H E S E S
Specialists performing mastectomy should ensure that the woman is aware of

services available which can organise the fitting of a temporary or permanent
prosthesis (while some patients are suitable for immediate reconstruction, others
who have delayed reconstruction will need to use an external prosthesis in the
interim). Follow-up should include assessment of post-mastectomy wound
oedema, neuralgia, and radiation skin change or swelling that may impair the

correct fitting and use of an external prosthesis. Clinicians should also be aware
of the consequences of a poor fitting, such as postural pain.
There is little literature concerning consumer access to and satisfaction with the
current range of external breast prostheses.250
4 . 7 C O M P L I C AT I O N S O F S U R G E RY
Breast surgery requiring general anaesthesia has a low risk of complications. The
main risks are:
• post-operative wound infection
• haematoma
• deep venous thrombosis
Women who have other unrelated diseases may have increased risk associated
with anaesthesia. In appropriate cases, this increased risk should be discussed
prior to surgery.
Following mastectomy and axillary dissection, a woman may experience:
• seroma of the axilla (following axillary dissection) or skin flap
• pain in the upper medial aspect of the arm and chest wall
• impact of loss of the breast on body image, appearance and self-esteem;
• lymphoedema of the arm (following axillary dissection)—which can occur
at any stage, even years after treatment
• chest wall discomfort—which should settle within six months
Following breast conservation and subsequent breast irradiation, a woman may
experience:
• seroma of the axilla (following axillary dissection)
• breast oedema
• breast pain and/or chest wall pain—which may last from three months to
up to several years in some cases
• lymphoedema of the arm (following axillary dissection and/or
irradiation)—which can occur at any stage, even years after treatment
Following breast reconstruction, a woman may experience:
• partial necrosis (death of tissue) of a soft tissue reconstruction
• infection and delayed healing
• infection and rejection of a prosthesis (in prosthetic breast reconstruction)
• a second primary tumour in retained breast tissue
• weakness of the abdominal wall (where tissue is in the rectus flap method
of reconstruction)

Women should be clearly informed of these potential side effects when treatment
options are being discussed, so they may make an informed decision.
After either total mastectomy with axillary dissection or breast conservation with
axillary dissection, limitation of shoulder movement (particularly abduction and
elevation) may occur, usually during the first few weeks. Appropriate exercises
with or without physiotherapy will usually restore full function. Frozen shoulder
is a rare complication of these operations. Arm exercises to restore function
should be commenced on the first post-operative day.
When axillary dissection has been performed, it is usual to have some sensory
loss in the chest wall below or posterior to the axilla and in some cases on the
medial and posterior aspect of the upper arm. Preservation at the intercosto-
brachial nerve reduces the extent of sensory loss.
As a generalisation, radical surgery combined with radical radiotherapy to the
axilla results in a significantly increased risk of late complications such as
lymphoedema. The risk of morbidity from combined treatment is relatively
constant, while the benefits (a reduction in the risk of death and/or a
locoregional recurrence) increase the higher the risk of recurrence or death. The
matter becomes one of individual choice as it is obvious that not all women will
see these costs and benefits in the same light.
The predisposing factors to the development of lymphoedema remain poorly
understood. Analysis of research about the prevalence of lymphoedema is
complicated by the lack of comparability between studies and by methodological
problems in individual studies (see section 4.4).216
Evidence supporting many forms of proposed treatments for lymphoedema, such
as compression techniques, physical therapy, and surgical techniques, is less than
optimal.216,251 Higher quality research is needed to examine the most efficacious
treatments for this condition. (See NHMRC National Breast Cancer Centre
Lymphoedema: prevalence, risk factors and management: a review of research,
1997.)
Patients with lymphoedema are at high risk of psychological distress.252-254 A
special garment designed to compress the limb, and regular massage to the arm
may be recommended to reduce the swelling of lymphoedema; there is some
evidence of the effectiveness of these techniques (Level III).216 The management
of lymphoedema requires the input of both medical practitioners and
physiotherapists, and occasionally of occupational therapists.

Key point
Women who have lymphoedema, or who have had both
surgery and radiotherapy to the axilla resulting in a high risk of
developing lymphoedema, need to look after their arm as the
risk of infection is high. Women should be advised that the risk
of problems associated with lymphoedema may be decreased
by adhering to the following:
• if the arm on the same side as the surgery is cut or
infected, or becomes hot, red, or swollen, immediate
medical advice should be sought, the area cleaned and oral
antibiotics commenced at the earliest sign of infection
• if possible, avoid in the affected arm: having blood taken,
blood pressure checked, a drip inserted and an injection
or vaccination
• avoid cuts, burns and insect bites
• avoid washing the dishes without gloves
• avoid letting the arm become sunburnt
• avoid gardening without gloves and long sleeves
• avoid carrying anything heavy with the affected arm
• wear loose clothing and loose jewellery
• use skin cream to keep the skin of the arm moist
• keep cool during hot weather
• eat a healthy diet to maintain body weight within
reasonable limits
• undertake regular gentle exercise
Any intervention in the affected arm should be very carefully
considered.
Studies of the psychosocial impact of lymphoedema have found that

lymphoedema is associated with a diminished quality of life and that women with
lymphoedema may experience not just functional impairment but also
psychological morbidity.252,253,255 A recent review of the literature also reports that
studies have shown that women who develop lymphoedema exhibit higher levels
of psychological, social, sexual and functional morbidity than women with breast
cancer who do not develop this complication.256 The review concludes that it is
important that information about the condition and its consequences is given to
women early in the treatment cycle.256

4.8 THE ECONOMICS OF LOCOREGIONAL THERAPY
Breast conserving treatment is more expensive than mastectomy—three times as

expensive in one study257—because of the need for radiotherapy to prevent local
recurrence.257,258 However, these studies do not include the cost of reconstruction
after mastectomy, which may tend to equalise the cost.
While mastectomy may be the lower cost option in monetary terms, quality of life
is an important factor in the cost/benefit equation. If a woman believes that her
quality of life will be improved by choosing one treatment instead of another, that
choice confers a benefit and should, where possible, be met.259
4 . 9 P R AC T I C E AU D I T
The audit of practice outcomes provides valuable information for the clinician
and health service providers. Clinicians are encouraged to audit their practice.
The Royal Australasian College of Surgeons has a breast audit instrument for
breast surgeons (for further information see Appendix I). A national audit tool has
been developed for radiotherapy, and one for medical oncology is in the process
of development. (For the radiotherapy audit tool, please refer to Radiotherapy
and breast cancer. Prepared by the Radiation Oncology Advisory Group; NHMRC
NBCC and Royal Australian and New Zealand College of Radiologists, 1999).

CHAPTER 5 R A D I OT H E R A P Y
Radiotherapy has been used in the treatment of breast cancer since the late
1890s. Today it is used commonly after breast conserving surgery and less
commonly after mastectomy.
In 1995 the Early Breast Cancer Trialists’ Collaborative Group published a meta-
analysis of the results of randomised trials of radiotherapy and surgery.195 They
concluded that the addition of radiotherapy to surgery resulted in a rate of local
recurrence that was three times lower than the rate with surgery alone (Level
I).195 This meta-analysis was updated in 2000.228
However, they found no significant difference in 10-year survival: among a
total of 17,273 women enrolled in such trials, mortality was 40.3 per cent with
radiotherapy and 41.4 per cent without radiotherapy. Radiotherapy was
associated with a reduced risk of death due to breast cancer (odds ratio, 0.94; 95%
confidence intervals, 0.88–1.00) which indicates that after 10 years, there would
be about 0–5 fewer deaths due to breast cancer per 100 women. However, there
was an increased risk of death from other causes (odds ratio 1.24; 95%
confidence interval 1.09–1.42).
5 . 1 R A D I OT H E R A P Y TO T H E B R E A S T A F T E R B R E A S T
C O N S E RV I N G S U R G E RY
The routine use of radiotherapy following breast conservation has been

examined. In the Uppsala-Obrebro trial,260 women were selected on the basis of
mammographic findings, had tumours )2cm, were node-negative and had
pathologically confirmed free margins. There was a statistically significant
difference in favour of giving radiotherapy to reduce the risk of local recurrence
and consequent mastectomy. The five-year actuarial recurrence rate was almost
20 per cent in women receiving no radiotherapy, compared with less than 3 per
cent in women treated with radiotherapy. This local recurrence rate of almost
20 per cent has been shown to increase with time,261 as has been the case in
other randomised trials such as NSABP B06.262
In other studies involving women not so carefully selected, local recurrence
reaches almost 10 per cent per year within the first two years204 and 40 per cent
at eight years263 for breast conserving surgery without radiotherapy. The Uppsala-
Obrebro trial mentioned above has demonstrated clearly that even when CLE is
confirmed by meticulous histological examination in T1 tumours, the risk of local
recurrence is substantially increased if adjuvant radiotherapy is omitted.260
The success of an approach which conserves the breast depends on pathological
confirmation that the margins of the resected breast tissue are not involved by
the tumour. It is not necessary for the pathologist to verify that the margin is of a

specific dimension, for example, 10mm. Re-operation to obtain this degree of
clearance is not necessary but adds to cosmetic deformity.43,264
While it is not uncommon clinical practice to omit radiotherapy in highly
selected early cases, it has to be emphasised that the decision requires the
woman to weigh the benefits of avoiding the side effects and inconvenience of
radiotherapy against the risks of local recurrence and the possible need for later
mastectomy. A group of women at sufficiently low risk of local recurrence to
allow breast conservation without radiotherapy has not been defined. Sometimes
it may be appropriate to omit radiotherapy. Full discussion with the individual
patient is essential, including provision of information about the benefits and
potential risks of this course of action.
Although adjuvant radiotherapy is frequently omitted in the elderly woman, there
is no objective evidence to show that this does not incur an increased risk of
local recurrence.265
(Please refer to Chapter 4 for further information about the role of radiotherapy
in the management of the axilla).

evidence
Radiotherapy after complete local excision (CLE) is I 195, 260, 266

recommended as it significantly reduces the risk of
local recurrence in the breast and the need for further
surgery. It should not be omitted, even in
selected patients.
5 . 2 R A D I OT H E R A P Y A F T E R M A S T E C TO M Y
Radiotherapy to the chest wall and/or regional nodes is probably the most
controversial area covered in these guidelines. It has been traditionally given with
the dual aims of reducing local and regional recurrence and of improving
survival.
The vast majority of clinical trials which have addressed the role of
postmastectomy radiotherapy have done so when the radiotherapy has routinely,
rather than selectively, followed surgery.
Studies such as the King’s Cambridge trial229,267 and the Edinburgh trial268 have
shown the importance of treating the axilla. Both studies revealed a significant
increase in uncontrolled local recurrence when simple mastectomy and
observation were compared with simple mastectomy and radiotherapy
(Level I).269
Impact of postmastectomy radiotherapy on survival
Several meta-analyses have examined trials of postmastectomy radiotherapy.
Interpretation of the results of these meta-analyses is difficult because of changes
over time in radiotherapy techniques.
The National Breast Cancer Centre’s Radiation Oncology Advisory Group (a joint
group with the Royal Australian and New Zealand College of Radiologists)
commissioned a further meta-analysis of trial data that would include the most
recent information from those Danish and Canadian pre-menopausal patient
trials.269
Based on meta-analyses270-272 and a recently commissioned meta-analysis of trial
data269 which includes the most recent randomised controlled trials,220,221,227
several conclusions can be drawn:
• There is clear evidence of a significant reduction in the risk of local
recurrence following postmastectomy radiotherapy with the prevention of
approximately two-thirds of recurrences (Level I).269 There is no evidence
that the relative reduction in the risk of local recurrence varies according
to various risk factors including age, nodal status, receptor status, tumour
grade or tumour size.
• There is clear evidence of a reduction in the risk of breast cancer mortality
after postmastectomy radiotherapy (Level I).228,269
• The reduction in breast cancer mortality is offset to some extent by an
increase in the relative risk of death from causes other than breast cancer.
On balance, the evidence does not indicate a reduction in total mortality
following radiotherapy. There is also no evidence that the effect of
radiotherapy on mortality varies significantly according to the extent of the
surgery, type of radiotherapy, the year trials commenced or completed
recruitment, or whether or not systemic therapy was administered.228
• It is difficult to reconcile these findings; in particular, recent updates of two
of the trials show a statistically significant increase in survival in those
women receiving postmastectomy radiotherapy.220,221
The overview considered non-selective use of radiotherapy either as a definitive
treatment of the axilla or routinely as an adjuvant to definitive surgery. Logically,
even the latter trials should have been combined with the Danish and Canadian
studies. Furthermore, many of the older trials used obsolete techniques with little
regard to dose and fractionation. It is thus not surprising that when combined in
this way with all other trials, the important data provided by the updates of the
two trials fail to confirm a statistically significant reduction in mortality overall.

Summary of the evidence
Postmastectomy radiotherapy reduces the risk of locoregional
recurrence (Level I) and of cause-specific mortality
(Level I).228,269 The impact of postmastectomy radiotherapy on
all cause mortality remains unclear. A review of the most recent
published data273 has shown a reduction in all cause mortality,
but this is not supported by the results of the meta-analysis of
all randomised controlled trials.228 It is therefore logical to
recommend postmastectomy radiotherapy for those at high
risk of local or regional relapse. The risk threshold at which
radiotherapy should be considered will depend on the likely
benefit and on any possible adverse effects of that radiotherapy
(the latter may depend on age).228
Risk of locoregional relapse

Data that indicate the levels of risk of locoregional failure are difficult to obtain
from the 32 trials included in the third meta-analysis.269 However, evidence from
large, retrospective, well analysed series (Rutquivst personal communication,
1997) and a recent analysis269 would suggest that the following are important
indicators of increased risk of locoregional recurrence:
• increasing number of positive nodes
• increasing tumour size
• involvement of margins
• high histological grade of tumour
• lymphovascular invasion
While the existence of extracapsular spread is an indicator of poor survival,274 it
does not increase the risk of axillary recurrence.275,276 Another recent study has
questioned the value of extra nodal spread as an indication for radiotherapy to
the axilla (Level III).277

Summary
Postmastectomy radiotherapy may therefore be considered in
the following circumstances:
• tumours greater than 5 cm
• axillary involvement of more than three nodes
• the presence of positive tumour margins
In addition, when smaller tumours are found or fewer nodes
are involved but one or both of the following are present,
postmastectomy radiotherapy may be considered:
• lymphovascular invasion
• high grade — grade 3
More trials are required to establish the effect on overall survival of modern
radiotherapy after mastectomy. Until such data exist, prevention of local
recurrence remains an important goal of postmastectomy radiotherapy.
These issues are considered in detail in the publication Radiotherapy and breast
cancer278 developed by the Radiation Oncology Advisory Group of the iSource
National Breast Cancer Centre and the Royal Australian and New Zealand College
of Radiologists.

evidence
Postmastectomy radiotherapy is recommended for I 269, 228

women at high risk of local or regional relapse
5 . 3 C O M P L I C AT I O N S O F R A D I OT H E R A P Y
Radiotherapy has a number of early local and general side effects, as well as late
morbidity. The extent and severity of complications from radiotherapy will
depend mainly on:
• the anatomical extent of the radiation fields
• the field arrangement
• the fraction size
• the total dose

Side effects increase significantly where the fraction size is greater than 2Gy per
day, where the dose is greater than 60Gy and where other than megavoltage
therapy has been employed.
Radiation does not cause alopecia, unless directed at the head.
The studies examining adverse effects and quality of life are generally of poor
quality.279 However, to enable patients to plan their lives, they should be alerted
before treatment commences that tiredness, lassitude or fatigue during or
following treatment may be experienced.
Local effects that occur during treatment include redness and soreness of the
skin. These will extend over the area of treatment and may cause concern to
women. They usually resolve within a week or two of completion of treatment.
Later effects may occur in the months or years after radiotherapy, including tight
skin and lymphoedema (if the axilla is irradiated). Lymphoedema usually occurs
between six months and several years after treatment.
Side effects
• Lymphoedema
Lymphoedema can occur in any woman who has had either radiotherapy to the
axilla or lymph node dissection. It is far more common in women who have had
both (see section 4.4, Management of the axilla).
• Local side effects in the conserved breast

Women who have radiotherapy to the conserved breast may experience
abnormal sensation varying between discomfort and significant pain, particularly
in the first two years. The end cosmetic result is affected by many factors. The
most important determinant of cosmetic result is the extent of surgery, followed
to a lesser extent by the following factors:280,281
• the surgical technique and the positioning of the scars
• the dose of radiation
• the boost technique (boost to large areas runs the risk of producing
fibrosis and distortion)
• the extent of axillary dissection (level 1, 2 and 3 dissection may
increase oedema in the breast)
• size of the breast—the larger the breast, the more likely it is to show
a post-radiation shrinkage
• other factors such as weight gain, which may result in a
disproportionately small increase in the fat in the treated breast

There is conflicting evidence over whether chemotherapy given at the same time
as radiotherapy affects the cosmetic result.
Breast-feeding is generally not possible from the irradiated breast, but cases where
it has been possible have been reported.282
• Cardiac/vascular damage
A meta-analysis of trials of adjuvant postmastectomy radiotherapy showed that in
the 15+ year survivors, there was a non-significant increase in cardiac deaths.272
This segregated according to the side of the tumour and was related to inclusion
of the heart in the high-dose volume.
Modern planning techniques, designed to irradiate only the chest wall ± the
residual breast deliberately exclude the heart from dose volumes >10 per cent,
appear to decrease the risk of cardiac damage.283 A cohort study of women treated
with breast conserving surgery and post-operative radiation therapy found no
indication of an increased risk of acute myocardial infarction associated with the
radiation therapy.284 However, the study suggested that cardiac damage is related
to the volume of heart irradiated.285
This is supported by the analysis of morbidity and mortality data from two Danish
randomised controlled trials220,227 of post-mastectomy radiotherapy in high risk
breast cancer patients. When radiotherapy is delivered to the chest wall, axilla,
internal mammary chain and supraclavicular fossa and when due attention is paid
to minimising cardiac dose, ischaemic heart disease morbidity and mortality are
not increased at 12 years.286
In a more recent overview228 on the favourable and unfavourable effects of
radiotherapy on the long-term survival of breast cancer patients, once again both
breast cancer mortality and local recurrence were reduced. However other,
particularly vascular, mortality was increased. This hazard of increased morbidity
is most marked in women with a low risk of locoregional recurrence (and hence
unlikely to experience a major benefit from adjuvant radiotherapy) and in older
women.
• Osteitis of the ribs

This is a brittleness of the ribs which occurs in up to 2 per cent of cases287 and
can lead to spontaneous fracture. However, this usually requires no treatment. The
risk of stiffness of the shoulder can be reduced by appropriate shielding.
• Acute radiation pneumonitis

The risk of acute radiation pneumonitis is reported to range from 0.7–7 per
cent.287 When the breast and axilla are irradiated, the risk will be at the upper end
of the range because the risk increases with the amount of lung in the radiation
field. It is, therefore, a rare complication. Small asymptomatic radiological changes,

often referred to as fibrosis, may be noted on the chest X-rays. They may cause
confusion and may be mistaken for metastases.
• Brachial plexopathy
This is a very rare complication and will only occur when the axilla and supra-
clavicular fossa are irradiated. The incidence is 0.3 per cent at five years with
current doses and fractionation,288 but has exceeded 5 per cent when
hypofractionated regimens have been used.289
• Second malignancy
Six studies involving about 150,000 women treated with radiotherapy have
reported on the development of a second malignancy.290 These studies have
shown a relative risk of 1.17 which was not statistically significant.
About half the series quote an increased incidence of colon, uterine and ovarian
cancer in patients irradiated for breast cancer.These cancers are unlikely to have
been caused by radiotherapy, as the host organ does not lie within the field
irradiated. When site-specific associations such as colon, uterus and ovary are
excluded, the risk of second malignancy becomes negligible in the clinical
context (Level III).290
In terms of post-radiation sarcoma, only 24 cases have been reported in seven
series involving nearly 34,000 patients with follow-up of 5–18 years. The best
estimate of risk is of two cases of post-radiation sarcoma per 10,000 women years
of follow-up. In the case of breast conservation, perhaps half of these cases will
be an angiosarcoma of the breast.291
Key points
The prescription of radiation and the techniques used to
deliver it can be extremely complex.
The radiotherapeutic management of breast cancer following
breast conservation is governed by two fundamental
radiobiological principles. These are that:
• The tolerance of normal tissue is a function of the total
dose of radiation received as well as of the dose received
per fraction per day and the volume of tissue irradiated.
• The probability of eradicating disease is a function of the
dose delivered and the magnitude of the disease burden
— in other words, a larger dose is required to eradicate a
larger tumour given equal radiosensitivity.

Radiotherapy after breast conservation involves irradiation of
the whole breast with a moderate dose, often followed by a
higher dose, or boost, to the site of excision of the primary
lesion. The boost allows the delivery of a higher dose to a small
volume within which the risk of residual tumour is greatest.
The side effects of radiotherapy are a function of the total dose,
the number of fractions in which it is delivered (that is, dose
per fraction) and the time over which it is delivered. It is
possible to give radiotherapy more quickly than the usual five
to six week schedules, but this would require a reduction in the
total dose given, which may reduce its efficacy. It would also
require giving larger doses each day, which could increase the
risk of late tissue damage and poor cosmesis. Recent evidence
suggests that shortened radiotherapy fractionation schedules
can achieve high rates of local control with acceptable
cosmesis.292 Long-term results and additional results are
awaited.
Chemotherapy given in conjunction with breast radiotherapy
may increase morbidity (for example, anthracycline may
increase risk of cardiac damage and concurrent chemotherapy
may increase risk of acute skin toxicity). However, preliminary
results indicate that radiotherapy can be given with
cyclophosphoamide, methotrexate and 5-fluorouracil (CMF)
therapy.292,293
These issues are considered in detail in the publication Radiotherapy and breast
cancer278 developed by the Radiation Oncology Advisory Group of the iSource
National Breast Cancer Centre and the Royal Australian and New Zealand College
of Radiologists.

CHAPTER 6 S Y S T E M I C A D J U VA N T T H E R A P Y
Systemic adjuvant therapy includes all forms of hormonal manipulation and/or

cytotoxic chemotherapy administered in conjunction with local therapy for early
breast cancer.The aim of such therapy is to treat undetectable remaining cancer,
which will reduce the risk of clinically evident metastatic disease and local
recurrence. Ultimately, this should improve survival. This is a rapidly evolving area
of knowledge, and many new agents are currently in trial. As new data emerge
this section will be updated. Decisions regarding adjuvant systemic therapy are
most appropriately made in a multidisciplinary setting.
Key to evaluating the potential impact of adjuvant therapies is an assessment of
the absolute risk of recurrence for individual women. Several prognostic
formulations have been developed64 based primarily on tumour size, grade and
extent of nodal involvement. Data are also available from control groups in
randomised trials of adjuvant therapy, published in overviews.297-298 These groups
however may not represent the general population at risk, as they have been
selected by trial entry criteria. Patients with small (<2cm), screen detected, node
negative tumours are under-represented in these trials and will be expected to
have a better outcome.
Overall survival at 10 years
Age <50 Age 50–69

Node negative 71.9% 64.8%
Node positive 41.4% 46.3%
Data from Early Breast Cancer Trialists’ Collaborative Group, 1998.298
There is strong evidence based on meta-analysis of all available randomised

clinical trials294-298 to show that adjuvant systemic therapy with the anti-oestrogen
tamoxifen reduces risk of recurrence and death after treatment for stage I and II
breast cancer in women with oestrogen receptor positive tumours up to the age
of 70 (Level I).297 In women aged under 50, ovarian ablation can offer similar
benefits (Level I).299 There is now good evidence that the benefits of tamoxifen
are limited to those patients whose tumours contain hormone receptors (either
oestrogen or progesterone receptors),297 and some evidence that the benefits of
ovarian ablation are similarly restricted.299,300 Many clinical trials use age, usually a
cut-off of 50 years, as a surrogate for menopausal status. Given that the median
age of menopause in Australia is about 52 years, this is not accurate. Those
recommendations that are based on age should be viewed with caution if they
exclude an assessment of the woman’s menopausal status. For example,
oophorectomy may be useful for pre-menopausal women independent of age.
Tamoxifen can be recommended for suitable women regardless of age.
There is also evidence from meta-analyses294-298 that multi-agent chemotherapy
also reduces the annual risk of recurrence and death in women with both node
positive and node negative disease up to the age of 70 years. The average
magnitude of these protective effects was approximately 25–30 per cent
reduction in risk of recurrence, and approximately 15–20 per cent reduction in
risk of death. It is important to look at these figures in terms of absolute
reduction in risk.
For a given proportional benefit in death (or recurrence) rate, the absolute
improvement in 10-year survival (or disease-free survival) will generally be
greater for women at higher risk. In the trials included in the overview, the
absolute difference in 10-year survival was about two-fifths of the proportional
reduction for women with node positive disease, and one-fifth for those with
node negative disease. Thus a 25 per cent reduction in death rate with treatment
might correspond to a 10 per cent absolute difference for women with node
positive disease, and 5 per cent for those with node negative disease.297 A smaller
absolute reduction (approx 2 per cent) would be expected in the hypothetical
good prognosis subset of node negative disease.

evidence
Under the age of 50 years (pre-menopausal women), I 299

ovarian ablation reduces the risk of recurrence and death
for women with breast cancer.*
Up to the age of 70 years, multi-agent chemotherapy I 298
reduces the risk of recurrence and death for women
with breast cancer.*
* See Table 5 for information regarding nodal status.
Factors which may affect the magnitude of benefit from each form of systemic
adjuvant therapy are considered below.
Before treatment begins, women who have not yet had children may wish to
consult with an obstetrician to consider their future options for fertility.
6 . 1 P R E - O P E R AT I V E C H E M OT H E R A P Y
There have been a number of studies301,302 of chemotherapy given prior to

definitive local treatment. In general, there is no additional benefit over the use of
chemotherapy after surgery in terms of disease-free or overall survival.

There is Level II evidence301 that this procedure can increase the overall breast
conservation rate from 60 to 67 per cent.The greatest increase was noted in
women with tumours greater than 5 cm in size. However, the rate of negative
nodes is increased and therefore some prognostic information is not available.
This approach is not recommended except in restricted circumstances,
particularly when breast conservation is sought in the presence of a large
tumour.
6 . 2 P O S T- O P E R AT I V E A D J U VA N T C H E M OT H E R A P Y
Evidence has shown that moderately prolonged (several months) combination
chemotherapy is more effective than single agent therapy and treatment lasting
less than one month (Level I).295 Accordingly, analyses in the Oxford overviews
have concentrated on trials of moderately prolonged combination chemotherapy
in which treatment lasted at least several months (mostly 6–12 months). Within
this range, duration of therapy had no apparent impact on outcome.298
The most recent Oxford overview confirmed a highly significant improvement in
recurrence-free survival, with absolute differences in 10-year recurrence-free
survival ranging from 5.4% –15.4% in the various groups (see Table 2).The main
divergence was observed during the first 5 years, with the curves remaining
roughly parallel thereafter. Absolute improvements in overall survival ranged from
2.3–12.4% (see Table 2).The beneficial effect of chemotherapy on overall survival
continued to increase between 5 and 10 years, especially in women aged under
50.
Table 2: Chemotherapy: effect on outcome
Age Relative Nodal Absolute difference

risk reduction status at 10 years
Recurrence-free survival All 24%
<50 35% Node negative 10.4%
Node positive 15.4%
50–69 20% Node negative 5.7%
Node positive 5.4%
Overall survival All 15%
<50 27% Node negative 5.7%
Node positive 12.4%
50–69 11% Node negative 6.4%
Node positive 2.3%

The data above were averaged over all chemotherapy combinations, with some
proving more effective than others. In the most recent analysis, the combination
of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) was not
significantly different from all other regimens combined. However, variations exist
between CMF regimens, with some given entirely intravenously,303 though the
classical CMF regimen uses cyclophosphamide by mouth.
There is no direct randomised comparison between CMF using oral or
intravenous cyclophosphamide in the adjuvant setting. One European
Organisation for Research and Treatment of Cancer (EORTC) randomised clinical
trial of women with metastatic breast cancer304 reported superiority for the
combination using oral cyclophosphamide, and a similar trend was reported in
comparisons of adjuvant studies.305,306 In the absence of definitive data, the
classical combination with oral cyclophosphamide is preferred where practical.
In the updated Oxford overview,298 the quantitative benefit of adjuvant cytotoxic
therapy in women aged 50–69, although still highly significant, was about half the
magnitude seen in younger women.
Anthracyclines were more frequently used in the newer trials included in the
recent overview. This allowed the analysis of anthracycline-containing regimens
against CMF. Anthracycline-containing regimens gave slightly superior results
when compared to CMF, both for recurrence-free survival (risk reduction 12%
SD=4; absolute difference at 5 years 3.2%; 2p=0.006) and overall survival (risk
reduction 11% SD=5; absolute difference at 5 years 2.7%; 2p=0.02) (Level I).
However, anthracycline-containing regimens are associated with increasing
toxicity, including complete alopecia and increased risk of cardiac toxicity,
particularly for patients receiving left-sided chest irradiation.298 This is also
supported by recent individual trials in pre-menopausal node-positive women307
and in high-risk node-negative women:308 both trials confirmed greater toxicity,
particularly febrile neutropenia. However, the overview noted that results from all
trials exploring this issue were not yet available.
All the trials in the most recent Oxford overview commenced before 1990. They
do not allow assessment of the value of increased dose intensity.
Once perioperative and preoperative regimens were excluded, the Oxford
overview data found no evidence of a difference between cytotoxic regimens
lasting a few months and longer treatments.298 Choice of standard adjuvant
cytotoxic therapy outside of trials is now less clear than before the most recent
overview. It could reasonably consist of either 6 cycles of CMF (using oral
cyclophosphamide) or 4 cycles of adriamycin and cyclophosphamide (AC).
However, one recent study with short-term follow-up has shown improved
recurrence-free and overall survival in node-positive patients by the addition of
paclitaxel following four cycles of AC.309

evidence
Moderately prolonged (several months) combination I 295

chemotherapy is recommended as it is more effective
than single agent therapy and than treatment lasting
less than one month.
Anthracycline-containing regimes are superior to I 298
cyclophosphamide, methotrexate and 5-fluorouracil
(CMF) for both recurrence-free survival and overall
survival at the increased risk of alopecia, cardiac
toxicity and febrile neutropenia.
Dose reduction
Because of the side effects of cytotoxic chemotherapy, there is a temptation to
use lower doses. Retrospective analyses had suggested that lower doses were less
effective (Level III),310 but the potential for bias made interpretation difficult.
However, a large prospective randomised trial311 found that patients randomly
assigned to higher doses of 5-fluorouracil, doxorubicin and cyclophosphamide
(FAC) did better than those assigned to half the dose (Level II). No colony
stimulating factor (CSF) support was required in the higher dose arm of this trial.
There is thus evidence (Level II)311 that dose intensity is important to outcome in
adjuvant cytotoxic therapy, at least in the range of doses achievable without CSF
support.
An alternative interpretation is that lower doses are ineffective.

evidence
Dose intensity is important to outcome in adjuvant II 311

cytotoxic therapy, at least in dose ranges achievable
without colony stimulating factor (CSF) support.

High-dose chemotherapy requiring stem cell support
Although trials are in progress to compare high-dose and conventional
chemotherapy,312 few have yet reported results. Weak evidence based on a
historically controlled series (Level III)313 suggests the use of high-dose therapy
requiring autologous bone marrow or peripheral blood stem cell support in
women at high risk of recurrence, such as those with 10 or more involved lymph
nodes. However, two small randomised trials have not shown benefit for high-
dose therapy (Level II).314,315
Such therapy is expensive and potentially hazardous, although the initially high
rates of toxic death have fallen with increasing experience of the technique.
However, the use of high-dose chemotherapy remains controversial. A recent
review of research into this area concluded that firm evidence is needed of the
benefit of this treatment compared with conventional therapy.316 Currently there
is insufficient evidence to justify the delivery of high-dose chemotherapy to
women with breast cancer outside of clinical trials.316

evidence
Treatment with high-dose chemotherapy outside of II 314, 315

clinical trials is not recommended.
Granulocyte-colony stimulating factors

The evidence regarding the correct use of granulocyte-colony stimulating factors
(G-CSFs) is still accumulating. Guidelines recently prepared by the American
Society of Clinical Oncology for the use of G-CSF support317 concluded that
primary use of G-CSFs should be restricted to cytotoxic regimens expected to
produce febrile neutropenia in at least 40 per cent of the patients treated. Since
these levels are unlikely with conventional adjuvant cytotoxic therapy doses,
routine G-CSF support is not recommended.
Secondary use of G-CSFs in patients who have experienced febrile neutropenia or
whose therapy might otherwise be delayed or given in lower dosage because of
neutropenia has been suggested, but remains of unproven value.
G-CSF support may be considered as an alternative to dose reduction in patients
with a history of febrile neutropenia.

Side effects of cytotoxic chemotherapy
Nausea, vomiting, tiredness and alopecia are the side effects most frequently
associated with cytotoxic therapy.318 Newer anti-emetics have reduced the
severity of nausea and vomiting.319,320
Temporary alopecia sufficient to require a wig is common following
anthracyclines,321 although less common in women having CMF.322 Alopecia may
be very distressing for the woman and her family, as it is a highly visible reminder
of the cancer for which she is being treated. Although hair usually grows back
within three months of completing treatment, it may have a different texture and
be curlier than before.
Chemotherapy has been associated with long-term impairment in sexual function
and infertility associated with premature menopause323,324 (Level III), with studies
reporting between 50–60 per cent of women treated for early breast cancer
having sexual dysfunction beyond 12 months post-treatment.325,326 The causes of
this may be direct, through gonadal and hormonal effects, and indirect, through
fatigue, apathy, nausea, vomiting and sleep or appetite disturbances that interfere
with libido.327 Change in sexual function is more evident in those women who
become menopausal following chemotherapy,323 and this is a concern raised by
women.328
Tiredness is another side-effect that may undermine the woman’s ability to cope
with family and other responsibilities, particularly if it persists after completion of
chemotherapy. Another source of concern for women is the subjective sense of
impaired thinking and poor concentration following chemotherapy.There is
limited research in this area, but one study reported cognitive impairment in
75 per cent of women who had completed 3–18 months treatment with CMF,
CAF or tamoxifen.329 High-dose chemotherapy appears to impair cognitive
functioning more than standard-dose chemotherapy.330 Another study found that
patients with breast cancer treated with adjuvant CMF have a significantly higher
risk of late cognitive impairment than breast cancer patients not treated with
chemotherapy.331 These effects included problems with concentration and with
memory.
Less common short-term side effects include mucositis, diarrhoea, conjunctivitis,
chemical cystitis and anxiety about attending for treatment. Rarer side effects
include febrile neutropenia, infection, venous thromboembolism and
haemorrhage.318
In the longer term, therapy-induced leukaemia is rare.332
The risk of death from adjuvant chemotherapy is very low.
Congestive cardiac failure is associated with higher cumulative doses of
anthracyclines such as those of >500mg/m2 of doxorubicin or >900mg/m2 of
epirubicin. It may be exacerbated by radiation therapy which includes the heart.

It is important that women should be fully informed of the short- and long-term
effects of cytotoxic chemotherapy and of these potential side effects, including
impact on body image and sexuality (Level III),333 as well as of the potential
benefits of treatment. The provision of information on treatment and treatment
side effects improves emotional wellbeing (Level I).120
For information on menopausal symptoms see Menopause and hormone
replacement therapy: a booklet for women, 1996 NHMRC and Hormone
replacement therapy for peri- and post-menopausal women: booklet for health
professionals 1996, NHMRC.

evidence
Women should be fully informed of the short- and III 333

long-term effects of cytotoxic chemotherapy on
general functioning and on body image, sexuality
and fertility.
6 . 3 T A M OX I F E N
In the most recent Oxford overview,297 tamoxifen was associated with a highly
significant improvement in recurrence-free survival in women with ER-positive
tumours. It was recognised that tamoxifen had little benefit in patients with ER-
negative tumours. Analysis was therefore confined to those women whose
tumours were ER-positive or unknown.
The magnitude of the benefit of tamoxifen was clearly dependent on the duration
of adjuvant tamoxifen therapy, as shown in Table 3.
As with cytotoxic therapy, the main divergence in recurrence-free survival was in
the first five years, while overall survival advantages continued to accrue during
the second five years.

Table 3: Tamoxifen duration: effect on outcome
Tamoxifen duration Recurrence-free survival Overall survival

Risk reduction Absolute % Risk reduction Absolute
% difference at 10 yrs % difference at 10 yrs
Node negative
~ 1 year 17 ± 8 4.7 13 ± 8 3.4
~ 2 years 28 ± 5 5.6 11 ± 6 2.2
~ 5 years 49 ± 4 14.9 25 ± 5 5.5
Node positive
~ 1 year 21 ± 3 7.5 12 ± 4 4.5
~ 2 years 30 ± 3 10.0 19 ± 3 7.2
~ 5 years 43 ± 5 15.2 28 ± 6 10.9
Most trials used a tamoxifen dose of 20mg/day.There is no evidence that higher

doses offer better outcomes.294
In trials of one or two years duration of tamoxifen, there is a trend towards
greater improvement in recurrence-free survival among older women, but this
trend is weaker in the more recent trials involving about 5 years of adjuvant
tamoxifen, where the analyses are limited to patients with positive or unknown
ER. 297
There is strong evidence that adjuvant tamoxifen therapy reduces the incidence
of contralateral breast cancer (Level I).45,297 The protective effect is more marked
with longer periods of adjuvant therapy, and 5 years of tamoxifen approximately
halves this risk.This protective effect on contralateral breast cancer is similar in
women whose first breast cancer was ER-positive or ER-negative.297
Tamoxifen’s weak oestrogenic action also induces an increase in bone mineral
density and altered blood lipid patterns. While these changes might lead to a
reduction in cardiovascular events and deaths, no such reduction could be
demonstrated (or refuted) in the most recent overview data.297
The Oxford overview concluded that currently available trial results still leave
substantial uncertainty as to whether tamoxifen should continue to be routinely
taken beyond 5 years.297

Side effects of tamoxifen
The best evidence about the side effects of tamoxifen comes from placebo-
controlled trials, such as the B14 trial conducted by the NSABP.45 While tamoxifen
was associated with increased risk of hot flushes and vaginal symptoms (dryness
and discharge), contrary to the impression from uncontrolled data it was not
associated with excess weight gain (Level II).46,47 Ocular toxicity has also been
reported334 as have ocular changes, but the latter are typically asymptomatic. The
NSABP Breast Cancer Prevention Trial has reported that rates of stroke,
pulmonary embolism and deep-vein thrombosis were elevated in women aged 50
years and over following treatment with tamoxifen (Level II).48
A more significant problem is the increased incidence of endometrial cancer in
post-menopausal women, about 1/1000/year.45,335-337 This effect was particularly
marked in the NSABP trial,45 which had an unexpectedly low incidence of
endometrial cancer in the placebo group, and in a Swedish trial involving a higher
tamoxifen dosage of 40mg/day.338 Among women receiving tamoxifen for
prevention of breast cancer, the incidence of endometrial cancer was increased
about 2.5-fold (Level II).339
Women on tamoxifen and their doctors should be aware of the risk of
endometrial cancer. Abnormal bleeding should be investigated promptly, and
although no good scientific basis for screening for endometrial cancer has been
established, women on tamoxifen therapy should be considered for annual
gynaecological review. Guidelines for the gynaecological surveillance of women
on tamoxifen have been produced by the Royal Australasian College of
Obstetricians and Gynaecologists. For more information on these guidelines refer
to Appendix D.
Given that a similar increase in endometrial cancer has been noted with the use
of unopposed oestrogen replacement therapy for menopausal symptoms,340,341 the
effect of tamoxifen may reflect its weak oestrogen agonist properties.
Although the incidence of endometrial cancer is increased by tamoxifen therapy,
and the increase may be greater with more prolonged therapy and tamoxifen
doses above 20mg/day, the overall risk based on Australian incidence figures
remains approximately 1 in 1000 women per year. Hysterectomy rates in the
population will affect this risk, and additional data will be emerging from ongoing
trials. This increased risk from endometrial cancer is vastly outweighed by the
protective effect of tamoxifen against recurrence of breast cancer.
Data from the overview297 and from the breast cancer prevention trial339 indicate
no increased risk of any other cancer among women taking tamoxifen.
Care should be exercised when tamoxifen is prescribed for patients taking
warfarin as the metabolism of warfarin342 is decreased, potentially leading to
haemorrahgic complications.

Other anti-oestrogens
A number of other selective oestrogen-receptor modulators (SERMS) are under
investigation. There are three studies in progress comparing toremifene with
tamoxifen in the adjuvant setting.343 There are no data comparing its efficacy and
toxicity to those of tamoxifen in this setting. Raloxifene is under investigation as a
chemopreventive agent.There are no adjuvant studies under way at present.

evidence
Tamoxifen is recommended for most women with I 297

oestrogen receptor positive tumours, as it significantly
improves recurrence-free and overall survival in
women of all age groups.
Tamoxifen reduces the incidence of contralateral I 297
breast cancer.
Women should be informed of the potential side II 45–48
effects of tamoxifen, including endometrial cancer,
stroke, pulmonary embolism, deep vein thrombosis,
hot flushes and vaginal dryness and discharge, but
not excess weight gain. For most women, the protective
effect of tamoxifen against the recurrence of breast cancer
will vastly outweigh the increased risk of side effects.
6 . 4 O VA R I A N A B L AT I O N
Ovarian ablation involves destroying the function of the ovaries. This can be done
by removing them surgically, by irradiating them or by suppressing their function
using luteinizing hormone releasing hormone (LHRH) analogues such as
goserelin.
Oophorectomy was the first effective systemic therapy for breast cancer.344 A
number of relatively small trials in the 1950s, 1960s and 1970s failed to show an
overall survival difference, so the method fell into disfavour.
The most recent Oxford overview included data from 12 of the 13 trials
comparing surgical or radiotherapeutic ovarian ablation to no treatment, or to
identical treatment without ablation. All these trials commenced before 1980.
Trials of chemical ovarian suppression, all of which commenced after 1985, were
not included.The trials involved 2102 women aged under 50 at randomisation,

among whom there were 1130 deaths and an additional 130 recurrences. At 15
years, recurrence-free survival was significantly improved in the group receiving
ablation (45% vs 39%; p=0.0007), as was overall survival (52.4% vs 46.1%;
p=0.001) (Level I).298,299 This effect was seen in both node negative and node
positive women; oestrogen receptor status was not measured in all trials.
Not all patients underwent axillary dissection.The benefit of ovarian ablation was
separately significant in patients assessed as being with or without axillary
involvement at diagnosis.
Trials in which ovarian ablation was compared to no treatment showed a larger
benefit than those in which chemotherapy was administered to both groups. In
these latter trials, the additional benefit of ablation was not separately statistically
significant (see Table 4), but the number of events was small, and there was no
statistically significant interaction between the efficacy of ablation with or
without chemotherapy. In this situation, the overall effect is more reliable than
the subset analysis.298,299
Table 4: Efficacy of adjuvant ovarian ablation in women under 50

years
Group Recurrence-free survival Overall survival

Risk reduction Absolute % Risk reduction Absolute
% difference at 10 yrs % difference at 10 yrs
All women < 50 18.5 ± 5.5 6.0 ± 2.3 18.4 ± 5.7 6.3 ± 2.3
Node negative 8.9 ± 4.2 5.6 ± 4.0
Node positive 13.4 ± 3.8 12.5 ± 3.9
No chemotherapy 25 ± 7 24 ± 7
Both chemotherapy 10 ± 9 8 ± 10
Data from Early Breast Cancer Trialists’ Collaborative Group, 1996.298,299
No significant benefit was seen among women aged 50 or over at

randomisation.298,299 Ovarian ablation is not indicated after the menopause.
ER status was available for most of the trials with chemotherapy (which were in
general more recent than those comparing ablation to no treatment). Among the
194 patients with ER negative tumours there was no evidence of benefit of
ablation on recurrence-free survival or overall survival, while among the 550
women with ER positive tumours, there was a trend for ablation plus
chemotherapy to be more effective than chemotherapy alone in both recurrence-
free survival (odds reduction 13 ± 11%) and overall survival (17 ± 13%), though
these differences were not statistically significant.

Evidence from one randomised trial indicated that ovarian ablation alone was
superior to cytotoxic chemotherapy in pre-menopausal women with positive
oestrogen receptors, while cytotoxic therapy was superior if the receptors were
negative (Level II).300 This finding underlines the importance of obtaining
receptor results in all cases. If it is accepted that ovarian ablation is more effective
in women with receptor-positive tumours, the average results from the overview
may underestimate the magnitude of benefit for such women.
The trials reviewed used surgical oophorectomy or ovarian irradiation to achieve
ablation. Laparoscopic oophorectomy has made the operation more acceptable to
some women.
LHRH agonists such as goserelin produce an endocrine status equivalent to that
of oophorectomy, but are reversible on cessation of therapy. Their use and
efficacy in the management of breast cancer is suggested by preliminary results
of recent clinical trials.345-349 The optimum duration of treatment by goserelin is
not known.

evidence
Ovarian ablation is more effective in women with II 300

oestrogen receptor positive tumours.
Adverse effects of ovarian ablation

Premature menopause is associated with significant vasomotor, sexual and other
problems associated with oestrogen depletion, including increased risks of
osteoporosis and cardiovascular disease.The overall survival benefit in ovarian
ablation trials indicates that, at least within the first 15 years, the benefits of
therapy outweigh any such adverse effects.
The safety of oestrogen replacement therapy in women with breast cancer has
not been established.This is the subject of ongoing trials.
6 . 5 C O M B I N E D M O DA L I T I E S
Much of the evidence for the value of using more than one adjuvant modality is
indirect. Current clinical trials are addressing many questions about the
combination of cytotoxic and endocrine treatments in various sub-groups of
patients.

Does chemotherapy add to ovarian ablation?
Few trials have yet examined the need for cytotoxic adjuvant therapy in women
receiving ovarian ablation.
Does ovarian ablation add to chemotherapy?

As noted above, there is insufficient evidence in the most recent Oxford overview
to be certain. Although the impact of ovarian ablation appeared to be smaller in
the presence of cytotoxic therapy, the interaction was not significant.
The most influential single trial was the Ludwig Breast Cancer Study,350 which
supports the concept that the additional effect of ablation in the presence of
chemotherapy may be greater in women with ER positive tumours.
Does chemotherapy add to tamoxifen?

Both in patients aged <50 and in those aged 50–69, the overview data298 suggest
that the effects of tamoxifen and cytotoxic therapy are independent, so that the
proportional benefits of chemotherapy on recurrence-free and overall survival are
similar in the presence or absence of tamoxifen. A systematic review showed that
trials comparing anthracycline-containing chemotherapies or ‘classical’ CMF351 in
combination with tamoxifen yielded better outcomes than tamoxifen alone
(Level I),352 while trials using modified ‘CMF’ regimens showed no benefit.305,352

evidence
Chemotherapy in combination with tamoxifen yields I 352

an increase in disease-free survival compared with
tamoxifen alone.
Does tamoxifen add to chemotherapy?

The beneficial effect of 5 years of adjuvant tamoxifen was similar in trials of
tamoxifen versus nil, and in trials of tamoxifen plus chemotherapy versus
chemotherapy alone.297

evidence
Tamoxifen in combination with chemotherapy yields I 297

an increase in disease-free survival compared with
chemotherapy alone.
6 . 6 W H I C H WO M E N S H O U L D B E O F F E R E D S Y S T E M I C
A D J U VA N T T H E R A P Y ?
Because systemic adjuvant therapies have been proven effective, they should be
considered in the management of all women with high or moderate risk of
recurrence after local therapy for early breast cancer.
In deciding whether or not to recommend such therapy to a woman, the
potential benefit of systemic adjuvant therapy should be considered together
with her age, general health and preferences. In determining the value of systemic
adjuvant therapy, clinicians must initially determine prognosis without systemic
adjuvant therapy. 64
Tables 2, 3 and 4 summarise the estimated benefits of systematic adjuvant therapy.
Table 5 categorises the risk of recurrence associated with various prognostic
factors. Table 6 matches these risk categories with recommended systemic
adjuvant therapy. Systemic adjuvant therapy should be recommended to most
women with involved axillary nodes, because this is an indicator of a high risk of
recurrence after treatment for early breast cancer.
Women with node-negative breast cancer include a spectrum from those with
large, high grade, receptor-negative tumours whose prognosis is similar to
patients with involved nodes, to those with tiny, screen-detected tubular cancers
with a very low risk of recurrence. At the 1998 St Gallen meeting, a classification
of node-negative patients into low-, intermediate- and high-risk groups was
adopted (see Table 5).353
Tamoxifen and ovarian ablation are not in general recommended for women with
ER and progesterone receptor (PgR) negative tumours.Tamoxifen may be
considered in women whose tumours, although classified as receptor-negative,
contain some evidence of ER or PgR.353

Prognostic indicators
The size of the primary tumour affects the prognosis among node-negative
women (Level III).66 Women with ER-negative tumours have a poorer prognosis
(Level II).354,355
6 . 7 R E C O M M E N DAT I O N S
Clinical trials
Further delineation of optimum treatments for different subgroups requires that
as many women as possible be entered into appropriately designed and approved
clinical trials. These trials should seek to refine the indications for particular
therapies or combinations of modalities in the various subgroups defined by
patient and disease characteristics.
Treatment outside clinical trials

The willingness of patients to undergo adjuvant cytotoxic therapy is influenced
by their family and social status and by the details of the treatment, but not (at
least within a group who had all received treatment) by their age, educational
level, employment status or the use of concurrent adjuvant endocrine therapy. In
a study, women who had undergone adjuvant cytotoxic therapy regarded it as
worthwhile for relatively small absolute improvements in survival.356
Selection of higher-risk node-negative women for adjuvant systemic therapy
involves balancing the expected gains against the adverse effects. Detailed
suggestions are tabulated below.
The following suggestions for adjuvant systemic therapies outside clinical trials
are adapted from those defined at the 1998 St Gallen Adjuvant Breast Cancer
Conference. Note that menopausal status per se is no longer a major deciding
factor in the selection of adjuvant therapy, although the toxicity of therapy must
be balanced against its efficacy, especially in older patients.The evidence supports
the following general guidelines for women up to the age of 69. Borderline
situations require a careful discussion of risks and benefits between the patient
and the responsible clinician.The role of newer therapies, such as taxanes and
aromatase inhibitors, and prognostic markers, such as Her2 status, have yet to be
fully evaluated,386 and this section will be updated as results come to hand.
Table 6 has been arrived at on a consensus basis but some clinical experts believe
this could lead to over treatment of some women. For example, a woman with a
grade 1, node-negative 2cm carcinoma would be classified as being at
intermediate risk according to the St Gallen recommendations and ovarian
ablation with or without chemotherapy would be advised if the woman was

oestrogen receptor or progesterone receptor positive. Using the Nottingham
group recommendations the same woman would have an index of 2.4, which
approximates that of women in the general population, and adjuvant treatment
would not be advised. Before embarking on either course, the benefits of both
approaches should be discussed with the woman and the possibilities carefully
explained.
Table 5: Definition of risk categories for patients with node-negative

breast cancer
Factors Minimal/low risk Intermediate risk High risk

(all of the (at least one
listed factors) of the listed factors)
Tumour size* )1cm 1.1–2cm >2cm
Oestrogen receptor (ER) Positive Positive Both negative

and/or progesterone
receptor (PgR) status**
Grade Grade 1 Grade 1–2 Grade 2–3

(uncertain relevance
for tumours )1cm)
Age*** *35 years < 35 years
* It was generally agreed that pathological tumour size (of the invasive component) was the
most important prognostic factor for defining additional risk of recurrence.
** Oestrogen receptor (ER) and progesterone receptor (PgR) status are important biological
characteristics that identify responsiveness to endocrine therapies.
*** Patients who develop breast cancer at a young age are considered to be at high risk of
recurrence, although an exact age threshold for this increased risk has not been defined.
Younger women tend to have tumours of a higher grade and to have more positive nodes.

Table 6: Systemic adjuvant therapy recommendations outside clinical
trials353
Node negative
Patient group Minimal/low risk Intermediate risk High risk
Pre-menopausal Nil or Tamoxifen Tamoxifen Chemotherapy†
ER or PgR Positive ± Chemotherapy 1 + Tamoxifen
Ovarian ablation* Ovarian ablation*
LHRH analogue* LHRH analogue*
Pre-menopausal Not applicable Not applicable Chemotherapy
ER and PgR Negative
Post-menopausal Nil or Tamoxifen Tamoxifen Tamoxifen
ER or PgR Positive ± Chemotherapy 1 ± Chemotherapy 1
Post-menopausal Not applicable Not applicable Chemotherapy 2

ER and PgR Negative
Elderly Nil or Tamoxifen Tamoxifen Tamoxifen
± Chemotherapy ± Chemotherapy 3
Node positive
Patient group
Pre-menopausal Chemotherapy† + Tamoxifen
ER or PgR Positive Ovarian ablation or LHRH analogue ± Tamoxifen*
Pre-menopausal
ER and PgR Negative Chemotherapy †2
Post-menopausal
ER or PgR Positive Tamoxifen ± Chemotherapy1
Post-menopausal
ER and PgR Negative Chemotherapy2
Elderly Chemotherapy ± Tamoxifen2
* The St Gallen panel regarded these therapies as still being tested in clinical trials.
†
Anthracycline based therapies were superior to CMF in the overview 298
1
The addition of chemotherapy is effective,298 but consideration may be given to tamoxifen
alone in patients with relatively lower risk of recurrence.
2
The addition of tamoxifen may be considered in patients whose tumours show any evidence of
ER or PgR.
3
Add chemotherapy if no expression of ER or PgR in tumour.
6 . 8 T H E E C O N O M I C S O F S Y S T E M I C A D J U VA N T T H E R A P Y
The treatment of women with node-positive, pre-menopausal breast cancer with

systemic adjuvant chemotherapy is considered to be one of the most cost-
effective interventions in contemporary medical practice.357,358 It has been
estimated to cost US$1000 per QALY (quality adjusted life year).357
However the use of chemotherapy for node-negative women, who generally have
a lower risk of dying from breast cancer, is more controversial.257,357,359,360 While
treatment of these women is also beneficial, it is relatively expensive per life
prolonged or saved. It has been estimated to cost about US$50,000 per QALY.357
As well, data to determine which node-negative women will benefit from
chemotherapy are not available. With increasing use of screening mammography,
the proportion of women with uninvolved axillary nodes is likely to rise.360
Financial considerations become more important when considering the use of
tamoxifen. Using data from the Oxford overview, it has been suggested that
tamoxifen provides reasonable value for money in the treatment of women with
early breast cancer.361 Considering tamoxifen’s minimal toxicity, one of the main
disadvantages in treating women whom it will not benefit is monetary.
Overall, data concerning toxicities and impairment of quality of life during
systemic adjuvant therapy are insufficient to allow a true estimate of the cost of
toxicity from chemotherapy and time lost from work or other important parts of
life.257
The out-of-pocket expenses associated with adjuvant chemotherapy incurred by
women with or without private health insurance are discussed in the Centre’s
publication Out-of-pocket expenses incurred by women for diagnosis and
treatment of breast cancer in Australia (1999).259

CHAPTER 7 F O L L O W- U P
The follow-up procedures for women treated for breast cancer have evolved over
time362 with little data363 to validate the procedures employed. Surveys indicate
that the majority of recurrences are detected in the context of signs or symptoms,
and that a small percentage are detected in the asymptomatic phase.
It is desirable that follow-up procedures are defined to achieve specified
outcomes in a cost-effective manner. Women need to be informed of the goals of
follow-up. It should be reinforced that there is no evidence that intensive follow-
up improves survival. It is important that women understand the risks of
recurrence of disease, and that new symptoms should be assessed in the light of
this.
The notional goals of follow-up include:
• the early detection of local recurrence
• screening for a new primary breast cancer
• detection of treatment-related toxicities
• provision of psychosocial support
• identification of family history
The following discussion examines each of these goals, their utility to the patient
and the data supporting them.
E A R LY D E T E C T I O N O F L O C A L R E C U R R E N C E
With current treatment protocols,364 the in-breast recurrence rate is 1–2 per cent
per annum and 1 per cent after mastectomy. For women who have had
mastectomy, the majority of recurrences will be detected by clinical examination
alone. For women who have had breast conserving surgery, a significant
proportion will be detected by regular mammography.
The usual treatments for local recurrence—surgery and radiotherapy—are more
effective if used in the earliest phases.Treatment is aimed at maximising the
chance of long-term local control, as the effect of uncontrolled local recurrence
on the woman’s quality of life can be substantial.
Key point
Although there is a perception that early detection of distant
recurrence is desirable in order to commence treatment early,
this is based on the false notion that the goal of such therapy is
cure. Unfortunately, this is almost never the case.

There have now been two clinical trials365,366 involving more than 2000 women
with no survival benefit for women followed intensively compared to those with
a minimal follow-up schedule. One of these studies showed no increase in quality
of life from an intensive follow-up schedule (Level II).366

evidence
A minimal follow-up schedule is recommended, II 365,366

as there is no evidence that frequent intensive
follow-up confers any survival benefit or increase
in quality of life.
S C R E E N I N G F O R A N E W P R I M A RY B R E A S T C A N C E R
A history of breast cancer increases the risk of a second primary breast cancer
two- to five-fold.367 Approximately 5–10 per cent of US women with a first breast
cancer have been estimated to develop a second primary breast cancer during
their lifetime; half of these cancers will occur in the contralateral breast.367 This is
much higher than the incidence in the general population for whom regular
screening mammography is recommended. Accordingly, regular (at least annual)
mammography is strongly recommended.368
D E T E C T I O N O F T R E AT M E N T- R E L AT E D TOX I C I T I E S
Follow-up of patients affords opportunities for clinicians to review and reflect on

their practice and to assist with maintaining high quality clinical care. Audit of
patient outcomes can provide valuable data on the occurrence of treatment-
related toxicities and also contribute to an understanding of treated breast cancer
disease.
Lymphoedema
Lymphoedema of the arm occurs after either surgical axillary dissection or
radiation or both (see Chapter 4, Section 4.4). Regular follow-up is unlikely to
detect this before being noted by the woman. However, the opportunity can be
taken at follow-up visits to remind women of the need to avoid injury to the
upper limb or to assess any change and refer for treatment and management.

Systemic adjuvant therapy
Early complications of adjuvant chemotherapy include premature ovarian failure
causing menopausal symptoms, which may be distressing. Premature onset of
menopause as a result of such treatment may significantly influence sexual
functioning, body image and self-esteem in women.328
Subsequently, the issue that arises for women is that of HRT. However, the use of
HRT in women who have been treated with breast cancer is controversial, and it
is currently not known whether oestrogen replacement therapy can be safely
given to these women.
Decisions about management of menopausal symptoms should take into account
both tumour-related factors and the woman’s wishes.
It is possible that the wider use of anthracycline-containing regimens may be
associated with delayed cardiac toxicity.
Long-term observation for such complications should take place in an organised
manner, preferably as part of a clinical trial so that valid conclusions can be
reached.
Tamoxifen
As previously described (see Chapter 6), there are now data to indicate that
tamoxifen therapy is associated with an increased risk of cancer of the
endometrium. The exact risk in the Australian context is uncertain, but overseas
reports show the incidence of endometrial cancer was increased about 2.5-
fold.339 No screening procedures are routinely recommended at present, but
enquiry should be made about symptoms at each visit.
Psychological morbidity
Depression and anxiety are common following diagnosis and treatment of breast
cancer, and may require specific pharmacological and/or psychological
interventions. Doctors should enquire about the woman’s mood and how she is
coping, as it is rare for women to seek psychological assistance themselves.369,370
P ROV I S I O N O F P S Y C H O S O C I A L S U P P O RT
There are data demonstrating a variety of long-term psychological sequelae to

treatment for breast cancer.These include episodes of depression and anxiety,
especially when the time comes to cease adjuvant systemic therapy.371 Difficulties
of body image and adjustment may be common. Anxiety does not necessarily
abate with longer survival.73,372,373 However, there are insufficient longitudinal data
to describe the long-term course of significant adjustment problems in women
with breast cancer.
Some women find regular check-ups psychologically reassuring;374 others
associate them with a reminder of their diagnosis, leading to increased anxiety
(Level III).375 Check-ups provide opportunities for routine assessment of the
emotional adjustment of both the woman and her partner, and to provide support
and offer referral or counselling should the need arise.
Further information is contained in the NHMRC iSource National Breast Cancer
Centre Psychosocial clinical practice guidelines: providing information,
support and counselling for women with breast cancer. 94
I D E N T I F I C AT I O N O F FA M I LY H I S TO RY
Follow-up provides an opportunity to assess the risk of breast cancer in a

woman’s family. Some women identified as high-risk for breast cancer may wish
to clarify the genetic risk of family members and be referred to familial cancer
clinics (see Chapter 1).
E C O N O M I C S O F F O L L O W- U P
Given the large numbers of women with diagnosed and potentially curable
cancers, the care of these women has a large impact on the health care dollar.
As noted above, intensive follow-up affords no survival benefit over a minimal
schedule.365,366 Intensive follow-up also consumes extra resources because of
dubious results of tests performed by protocol.34 However, it does have the
potential to improve the knowledge and care of women. Women in clinical trials
need to be followed up closely, and the cost of follow-up should be built into the
cost of the trial.
One study376 suggests that if American doctors had adopted a minimal
surveillance strategy, they would have saved the US health care system (which
covers about 250 million people compared to Australia’s 19 million) $US636m in
1990. By 2000 this annual figure was expected to rise to more than $US1 billion
(in 1990 US dollars).
W H O S H O U L D P E R F O R M T H I S F O L L OW- U P ?
With the involvement of various specialists as well as the GP in the treatment of

an individual woman, it is important that follow-up be coordinated to ensure
patients are not subjected to an excessive number of visits.
Each treating team should develop a protocol which will result in rational follow-
up procedures and provide information regarding the outcomes of particular
treatment programs. For example, this may include alternating visits every six
months between treating doctors in the first two years so that women see one or
other specialist each three months.
In some parts of Australia, follow-up of people with cancer is the responsibility of
the GP. Under such circumstances, it is essential that the medical practitioner is
aware of an appropriate schedule of follow-up, such as that described in these
guidelines. The minimal requirement for regular follow-up of a primary breast
cancer is a clinical review every three months for the first year, then six monthly
to five years, then an annual review thereafter (see Table 7). A UK randomised
controlled trial with an 18 month follow-up, in which women received routine
follow-up either in hospital or in general practice, found that general practice
follow-up of women with breast cancer in remission is not associated with
increase in time to diagnosis, increase in anxiety or deterioration in health-related
quality of life.377
It is essential that the woman’s current GP is kept informed of the outcome of
visits and of any investigations undertaken. To ensure adequate audit, it is
recommended that all involved clinicians be informed of each others’ activities.
Some women will change doctors over the many years of follow-up. It is essential
that sufficient details of her medical history are available to ensure continuity of
care.
Women should be aware that they will have mammography as part of their
follow-up and that they do not need to respond to invitations from BreastScreen
Australia.
Table 7: Recommended follow-up schedule183,365,366
1–2 years 3–5 years After 5 years

History and examination every three months every six months every year
Mammography at 6–12 months after every year every year
(and ultrasound if indicated) radiotherapy
for conserved breast
Chest X-ray
Bone scan only if clinically indicated

blood count and
biochemistry
Not every clinician involved in the care of a woman will be closely involved in her follow-up.
Symptoms should be assessed as they arise.
Women with early breast cancer should also be advised not to neglect other
aspects of their health care.
Note that this follow-up schedule may change, due for example to the detection
of recurrence or the development of other illnesses. The schedule needs to be
tailored to individual situations.
Although women taking part in a clinical trial may be subjected to variations in
these recommendations, many trial protocols currently prescribe a similar
schedule.
Information on the follow-up of women with advanced breast cancer is provided
in the NHMRC iSource National Breast Cancer Centre Clinical practice
guidelines for the management of advanced breast cancer, 2001.
CHAPTER 8 REQUIREMENTS FOR SPECIAL
GROUPS
8 . 1 W O M E N F RO M R U R A L A N D R E M OT E A R E A S
About 30 per cent of Australian women who develop breast cancer live in
regional, rural or remote areas. Women living in regional towns generally have
good access to a range of services. However, women living far from urban centres
sometimes have difficult choices. They must undertake treatment locally or travel
far from family and friends. In a recent study, rural women with breast cancer in
Australia reported spending an average of six weeks away from home.378 Many of
these women would prefer to be treated in their local or regional area, rather
than having to travel to a metropolitan centre. The cost of opting for local
treatment is that choices may be limited. Most women, apart from those in
remote areas, will have reasonable access to a surgeon who can operate on the
primary cancer, remove it and stage the disease.
Increasingly, some general surgeons in rural areas have undertaken the
considerable effort required to develop a special interest in breast cancer surgery.
All surgeons who elect to manage women with breast cancer should keep
themselves and their colleagues up to date with the current knowledge and
treatment of all aspects of the disease, including current clinical trials. An audit of
patient treatments and outcomes should also be maintained.
Particularly in rural and remote areas, GPs play a key role in the initial diagnosis
of women with breast cancer.They also have an ongoing and important role in
the women’s post-operative management, including clinical follow-up, and in
palliative care where that proves necessary.
With the exception of a few major towns, radiotherapy is not available outside
capital cities, and resident medical oncologists are usually not available. Given
that radiotherapy usually requires six weeks away from home, this influences
some women to opt for mastectomy instead of breast conservation plus
radiotherapy.This decision is often made for pragmatic, financial, work, family and
social reasons.
Rural/regional surgeons managing breast cancer need a close liaison or
networking with appropriate medical oncologists, radiation oncologists and a
‘breast surgeon’ in a metropolitan breast unit. Preferably, these should be doctors
who either visit their region or have a specific interest or expertise in breast
cancer management for rural women. For most rural women this should facilitate
effective and efficient multidisciplinary assessment and management. The
oncologist’s recommended systemic adjuvant therapy can usually be
administered locally and should not require travel.
Women travelling for treatment benefit from being accompanied by a carer who
can provide support during their time away. The costs of travel to a regional or
urban centre are financial hardship, social dislocation and emotional strain.
Women who have treatment away from home may also find that communication
between their local doctors and the treating specialists is not adequate.
Out-of-pocket expenses for women in rural and remote areas

A recent report examined out-of-pocket expenses incurred by women for
diagnosis and treatment of breast cancer in Australia.259 It found that compared
with their urban counterparts, women residing in non-urban, rural and remote
areas do not appear to incur substantially greater out-of-pocket expenses for
medical services involved in screening, diagnosing and treating breast cancer in
their region. However, the evidence does suggest that many such women travel to
urban or metropolitan areas in order to receive these services and therefore incur
additional travel and accommodation costs.259
A shortage of plastic and reconstructive surgical services in regional and rural
Australia may create a barrier for having reconstructive surgery. Again, the woman
may have to consider travelling for treatment if immediate reconstruction is
desired. (Appendix H lists breast cancer support services throughout Australia.)
Although most states have a travel and accommodation scheme, in current
practice many women do not receive the financial assistance to which they are
entitled.378 The treatment team should assist women to access adequate financial
support. It should be noted that there appear to be substantial differences in the
patient travel and accommodation assistance schemes run by state and territory
governments.259
8 . 2 C U LT U R A L I S S U E S
Qualitative research exploring the views of women from non–English-speaking

and indigenous backgrounds has highlighted a range of issues.378,379
These include:
• Cultural issues: Immigrant women and those from some cultural
backgrounds may have specific beliefs that affect their attitudes to
treatment. For example, in some communities, breast cancer is viewed as
fatal and/or shameful.The role of the woman’s religious beliefs and those of
her family should be explored.379,380
• Female providers: In some communities, women may have a strong
preference for care from a female provider.This is the case in some
indigenous communities where breast cancer is perceived as ‘women’s
business’. Special care should be taken with these women to discuss
treatment options and to provide female doctors where possible. The use of
Aboriginal Health Workers may also be of value in assisting indigenous
women during treatment.
• Use of interpreters: If the woman is not fluent in English, it is important
to use a qualified and appropriate interpreter, rather than a family or staff
member. Interpreters are available free of charge in both the public and
private sectors, although they must be booked in advance of any
consultation. A telephone interpreter through the Translating and
Interpreter Service (TIS) can usually be provided within a few minutes,
although it is preferable to give some notice (phone: 13 14 50).
• Provision of information: Women from non–English-speaking and
indigenous backgrounds need access to information about breast cancer.
Some states have a telephone information service for women who are not
proficient in English; state and territory cancer organisations can provide
contact details (phone: 13 11 20 for local information from state cancer
councils).
Although the Multicultural Breast Cancer Information Service
(MBCIS) is located at the NSW Cancer Council, women who live in other
states/territories are welcome to contact this service (1300 300 935).
Lesbian women and their partners may have special needs and
problems. These are addressed in more detail in the iSource National Breast
Cancer Centre consumer guide for women with early breast cancer (in
preparation).
(Refer to NHMRC iSource National Breast Cancer Centre Psychosocial clinical
practice guidelines: providing information, support and counselling for
women with breast cancer, 2000.)94
CHAPTER 9 AREAS WHERE RESEARCH IS
NEEDED
Since the House of Representatives Report on the Management and Treatment of

Breast Cancer in Australia,381 many of its recommendations related to research,
policy and the organisation of breast cancer care have been addressed. The
iSource National Breast Cancer Centre has been involved in many of these
activities, which include:
• developing clinical practice guidelines
• developing resources for undergraduate medical training, GPs and
consumers
• surveys of surgeons and consumers
• review of radiotherapy after mastectomy
• commissioning research and reviews on a wide range of topics (see
Appendix F), including the psychosocial needs of women with breast
cancer
• organising a rural surgeons program
• guideline implementation and dissemination
• convening a lymphoedema summit to ascertain research priorities into this
area
• providing communication skills training for health professionals
However, much more research is needed into breast cancer. Topics which have
been identified include:
• The disease:
• the pathogenesis of the disease
• women with metastatic disease
• risk factors and profile
• genetics of breast cancer
• sentinel node biopsy
• The impact of the disease and treatment:

• the impact of breast cancer treatment on quality of life
• the identification and development of interventions to assist women
in coping with body image changes
• whether or not participation in a support group improves survival
• the identification of women at high risk of a poor recovery
The Australian New Zealand Breast Cancer Trials Group (ANZBCTG) and the
International Breast Cancer Group (IBCG) are conducting a number of trials
investigating breast cancer treatment.
Below are listed completed or ongoing projects conducted by the iSource
National Breast Cancer Centre and relating to the impact of the disease:
• the psychosocial impact of breast cancer as it is measured by health
professionals: A literature review on the detection of psychological
problems is currently under way.
• the impact of breast cancer treatment on body image and sexuality:The
results of focus groups and interviews is currently in draft form.
• the psychosocial impact of breast cancer on families, including the
development and evaluation of resources for children and partners of
women with breast cancer: There is an ongoing series of projects from
1998, with reviews and interview-based projects examining the needs of
children and issues encountered by women in talking to/supporting their
families. A partners’ support resource has been developed, and current
work is focusing on the development and evaluation of informational
resources for adolescent children of women with breast cancer.
• lymphoedema prevention and treatment. A lymphoedema summit was held
in February 2000 to consider national research priorities on issues related
to lymphoedema.
(Further information is contained in the NHMRC iSource National Breast Cancer
Centre’s Psychosocial clinical practice guidelines: providing information,
support and counselling for women with breast cancer.)94
• Deciding on treatment:
• systematic literature reviews on the validity, reliability and utility of
clinical examination and mammography, breast ultrasound, fine
needle aspiration biopsy, core biopsy, open biopsy and frozen section
histology
• better markers of responsiveness to therapy, disease progression and
patient survival
• the optimal method of combining chemotherapy, hormonal and
locoregional therapy
• factors influencing participation in clinical trials
• Treatment:
• systematic literature review on CLE with axillary dissection
• HRT in women with breast cancer
• the cost-effectiveness of interventions in breast cancer
• the role of radiotherapy in women with small, well differentiated
tumours
• factors that mediate outcome
• The consumer view:

• the consumer perspective in the Australian literature
• consumer initiated research
• the experience of specific groups, such as women of non–English-
speaking backgrounds, Aboriginal and Torres Strait Islander women
and women of low socio-economic status
• the decision-making process and how it is affected by stress
• levels of support best able to assist adjustment
• Prevention:
• prevention trials, such as that involving tamoxifen
• screening in women aged 40–49
• what will help women at high risk
• Cost-effectiveness:
• the collection of Australian cost data to allow analysis of the costs of
treatment options
• appraisal of the impact of treatment options on quality of life
• Outcomes:
• collection of Australian outcome data relating to breast cancer
treatment
The iSource National Breast Cancer Centre is currently engaged in:
• targeted strategies to implement early breast cancer guidelines (for
example, randomised controlled trial of a quality improvement kit for
hospitals)
• a national demonstration project on multidisciplinary care in breast cancer
• developing and disseminating guidelines on advanced breast cancer; DCIS,
LCIS and AH; fine needle and core biopsy; and diagnostic imaging of the
breast.
APPENDIX A: DEVELOPMENT OF THE FIRST
EDITION (1995)
The need for procedures to ensure effective clinical practice and focus the health
system more directly on health outcomes was identified by both the National
Health Strategy and the Australian Health Ministers’ Advisory Council.
The National Health and Medical Research Council (NHMRC) subsequently
established a Standing Committee of the National Health Advisory Committee
(formerly the Health Care Committee) to undertake the task. Initially named the
Quality of Health Care Committee, the Standing Committee was later re-named
the Quality of Care and Health Outcomes Committee (QCHOC) to reflect its
emphasis on outcomes of care. QCHOC was given the task of:
• establishing a recommended national approach to the development of
clinical practice guidelines which are focused on improving patient health
outcomes
• working with the clinical colleges and other expert groups to encourage
and facilitate the development of such guidelines and outcome measures
by these groups
Having drafted guideline for clinical guidelines development,382 the Standing
Committee then set up a number of pilot working parties with the dual role of
developing clinical practice guidelines in selected areas and trialing the proposed
methodology for developing guidelines. The Standing Committee agreed on the
following criteria for selecting pilot projects:
• high health burden imposed by the disease
• high cost of treatment interventions
• the existence of significant variation in current practice for similar
conditions
• a reasonable expectation that guidelines would lead to an improvement in
the quality of care and health outcomes
• the existence of a receptive group interested in taking on the development
of guidelines for a particular issue of concern
• pilot projects should represent the four focus areas under the
Commonwealth Department of Human Services and Health’s National
Health Goals and Targets (currently cardiovascular health; cancer control;
injury prevention and control; and mental health)
• guidelines should be achievable: in some areas, guidelines cannot be
developed while in others, guidelines are not required
• given the rising costs of health care, the area chosen for guideline
development should offer some degree of potential for achieving
cost-effectiveness in treatment
The treatment of diagnosed breast cancer was selected for guideline
development because it met the above criteria, and because there were concerns
that knowledge of the treatment options was not well disseminated among health
professionals. It was also felt that not all women with breast cancer were being
presented with the range of appropriate treatment options, and that guidelines
would help women make informed choices.
T E R M S O F R E F E R E N C E F O R T H E W O R K I N G P A RT Y
A Working Party was established to draft the guidelines with the following terms
of reference:
• Undertake the development and implementation of clinical practice
guidelines for the treatment of breast cancer, following the procedures
recommended by the QCHOC’s draft first edition of Guidelines for the
development and implementation of clinical practice guidelines.2
• Provide advice on this process to the QCHOC.
M E M B E R S H I P O F T H E W O R K I N G P A RT Y
(FIRST EDITION, 1995)
Membership of the Working Party reflected the multidisciplinary nature of breast

cancer treatment. It comprised representatives from all aspects of clinical
practice as well as consumer and breast cancer support groups; nurses;
counsellors; and other related experts such as epidemiologists, health economists
and medical educators.
The Working Party had the following members:
Emeritus Professor Tom Reeve (Chair) Surgeon; Member, Quality of Care and
Health Outcomes Committee
Dr Roger Allison Radiation oncologist
Associate Professor Raja Bandaranayake Medical educator
Professor Bruce Barraclough Surgeon
Dr Michael Bilous Pathologist
Professor Alan Coates Medical oncologist
Ms Mary Draper Policy activist
Professor John Forbes Surgeon
Mr Colin Furnival Surgeon
Dr Michael Green Medical oncologist
Mr Tony Green Surgeon; expert on remote/rural access
issues
Dr Jane Hall Health economist
Associate Professor Les Irwig Epidemiologist
Dr Michael Jones Radiologist
Professor Allan Langlands Radiation oncologist
Associate Professor Donald Marshall Surgeon (reconstructive surgery)
Ms Marcia O’Keefe Engineer; breast cancer consumer
advocate (Deceased October 1997)
Ms Beverley Rees Nurse; counselling and support
Mr Ian Russell Surgeon
Dr Angela Rutherford General practitioner
Dr Raymond Snyder Medical oncologist
Professor Robert Sutherland Biologist
Dr Jane Turner Psychiatrist
Mr Michael Wertheimer Surgeon
Ms Marion Powall (observer) Health Advancement Division
Commonwealth Department of Human
Services and Health
Ms Jayne Ross Secretary, Quality of Care and Health
Outcomes Committee
Ms Jane-Ann Jones Executive Secretary, Working Party on
the Treatment of Diagnosed Breast
Cancer
Dr Mark Ragg Consultant writer and editor
The Working Party also maintained close links with other groups currently
working in this area, such as the Australian Cancer Network and the Clinical
Oncologist Society of Australia.
PURPOSE AND SCOPE OF THE GUIDELINES
In order to maintain achievable terms of reference, the Working Party confined its
scope to the management of early breast cancer, both in situ and invasive cancer.
However, some introductory information was also included.
The objective of the guidelines is to assist clinician and patient decisions by
providing a framework within which to apply clinical judgement and to consider
the needs of each individual woman. The guidelines are not rigid procedural
paths; rather, their objective is to ensure that clinicians and women are well
informed about the risks and benefits of the recommended interventions.
The full guidelines document covers best practice for the management of breast
cancer from the point of initial diagnosis. While it aims to be a document useful
for both health professionals and consumers, a separate book, derived largely
from the main document, has been produced specifically in order to provide
information for women who have breast cancer and their relatives.
The guidelines are based on the following key principles which form the basis of
QCHOC’s approach to guideline development and implementation:
• a proper evaluation of the latest scientific evidence
• a focus on the improvement of patient outcomes
• the adoption of a multidisciplinary approach which involves all
stakeholders, including consumers
Target audience
These guidelines were developed to equip the treatment team with evidence-
based recommendations for optimal management of early breast cancer care,
according to the needs of the individual.
Scope of the guidelines

Topics covered include general principles of care, preoperative examinations,
surgical management, the use of radiotherapy and systematic adjuvant therapy
and follow-up requirements in relation to early breast cancer.
Outcomes
The guidelines are aimed at improving health and quality of life outcomes for
women diagnosed with early breast cancer. Key outcomes may include the
following:
• reduction in recurrence rates
• decreases in morbidity and mortality
• improved quality of life and psychological wellbeing
• improved communication between patients and clinicians
• improved knowledge and access to information for patients
P RO C E S S E S E M P L OY E D
The Working Party approached the development of the guidelines by setting itself
four key tasks:
Task 1: Identification of the known clinical problems and areas of
uncertainty in each of the disciplines involved in breast cancer
treatment.
Task 2: Collection and review of the scientific evidence, including meta-
analyses, to identify best and most appropriate practice for the
various interventions in breast cancer treatment.
Task 3: Establishment of a sub-group to review the literature and gather
information on best practice from the woman’s perspective.
Task 4: Development of a glossary of technical terms in the breast cancer
area, for incorporation in both documents.
Most of the work of the Working Party was conducted out of session, with
meetings used primarily to identify the direction to follow and to review out-of-
session activity. A technical writer was then contracted to prepare the document
and draw all the information together in consultation with the Working Party.
Task 1
At initial Working Party meetings, various individuals and groups identified known
clinical problems or issues in their respective fields. A specialists’ sub-group was
then formed to advance the clinical group’s input to the guidelines in the
surgical, medical oncological and radiotherapy areas.
Task 2
A member of the Working Party, Associate Professor Les Irwig, conducted
systematic reviews of randomised controlled trials in the following areas:
• the treatment for early breast cancer: its effects on mortality and
recurrence, its impact on quality of life and the effects of intensive
monitoring of patients after initial treatment
• the impact of counselling and other psychological interventions on quality
of life
• the impact of radiotherapy on quality of life
The findings from these reviews were incorporated into the guidelines.
The Working Party decided that it was important to give a clear indication in the
guidelines as to the strength of the evidence for recommendations, and to
provide references where appropriate. The rating system is discussed in detail
under ‘Levels of evidence’ in the introduction to these guidelines, and evidence
which has been rated as either Level I or II is presented in tabular form
throughout the text.
Task 3
At the request of the Working Party chairman, a Women’s Perspective sub-group
of the Working Party was convened in order to identify key issues in breast
cancer treatment from the woman’s perspective. From their knowledge of the
literature and their experiences as users and providers of breast cancer services,
the sub-group identified a number of issues it believed to be relevant to the
process of guideline development.These included:
• information needs
• choice and control
• counselling and support
• communication between women and health care providers
• the treatment process
• treatment outcomes
• access issues
• recurrent metastatic disease
The sub-group then commissioned a search of the professional and consumer
literature which addressed these aspects. Treatment outcomes and quality of life
issues were excluded from the literature review because this aspect was included
in the overall meta-analysis of treatment undertaken for the Working Party,
discussed above.
Analysis of the literature elicited a number of principles which were
incorporated in the guidelines, thereby ensuring that the guidelines reflect the
preferences of women.
Task 4
All members of the Working Party contributed to the compilation of a glossary of
breast cancer terms, which forms an Appendix to both documents.
COSTING ISSUES
A preliminary review was undertaken of the existing literature on the economic

evaluation of breast cancer treatment. The review was not exhaustive, and
focused only on those articles which considered options for treatment discussed
in the guidelines. Cost-effectiveness information is included for locoregional
therapy, adjuvant therapy and follow-up care. However, only one of the studies
examined was Australian in origin, and population characteristics and costs (in
particular) are therefore likely to differ. Nevertheless, while the results cannot be
generalised to the local setting, there is some commonality in existing treatment
patterns. The information is therefore included as some indication as to where
further research in the Australian setting may be worthwhile.
LIST OF SUBMISSIONS RECEIVED FOR THE FIRST

EDITION (1995)
1. Dr Jonathan Serpell
2. Ms Mavis Tassicker
3. Prof Alan Rodger, The Alfred Healthcare Group, Alfred Hospital
4. Ms Ellen McIntyre, Lactation Consultant
5. Dr Joanna Dewar, Breast Cancer Consensus Statement Panel, Sir Charles
Gairdner Hospital, The Queen Elizabeth II Medical Centre
6 Mrs J Christine James
7. Prof Rob Sanson-Fisher, NSW Cancer Council, Education Research Program
8. Dr Graeme Morgan, Faculty of Radiation Oncology, St Vincent’s Hospital
9. Ms KM Tobin, Breast Cancer Support Service, Anti-Cancer Foundation,
University of South Australia
10. Ms Michele Kosky, Health Consumers’ Council, Western Australia
11. Mrs Elaine Henry, NSW Cancer Council
12. Ms Anne Weeden, Breast Cancer Support Service, NSW Cancer Council
13. Dr FJ Bonar, Bankstown-Lidcombe Hospital
14. Dr John Boyages, NSW Breast Cancer Institute
15. Prof Robert Burton, The University of Newcastle, Royal Newcastle Hospital
16. Mr Adam McLean, NSW Cancer Council, Cancer Information Service
17. Ms Beverley Hunt, Breast Cancer Support Service, Western Region
18. Ms Lyn Swinburne, Breast Cancer Action Group
19. Mr John Collins, Royal Melbourne Hospital
20. Dr Sandra Turner, Division of Radiation Oncology, Westmead Hospital and
Community Health Services
21. Ms Gail Sanz
22. Dr Neil Piller, The Flinders University of South Australia
23. Mrs Alison Burnard
24. Professor J Kearsley, the St George Hospital Cancer Care Centre
25. Dr S Roberts, The Wesley Cancer Care Centre
26. Dr Verity Cooper, National Health Advisory Committee
27. Ms Marilyn Kenny, City & North Eastern Breast Screen
28. Ms Judith Marchant
29. Mr Michael Mason, The Adelaide Lymphoedema Clinic
30. Dr Michael Barton,The Royal Australasian College of Radiologists
31. Mrs Anthea Eyres
32. Ms Victoria Cuevas,The Royal Melbourne Hospital, Essendon Breastscreen &
Principal Assessment Centre
33. Ms Beverley Mirolo, The Wesley Clinic
34. Ms Helen Varney, Breast Cancer Action Group
35. Dr Jane Vallentine, Breast Screening Service, St George Hospital
36. Dr Geoff Delaney & Dr David Christie, Division of Radiation Oncology,
Westmead Hospital and Community Health Services
37. Dr George Rubin, NSW Health Department
38. Ms Margaret Dean, National Advisor, Committee for the Early Detection of
Breast Cancer, Commonwealth Department of Human Services and Health
39. Dr R Smee, Institute of Oncology, Department of Radiation Oncology, Prince
Henry & Prince of Wales Hospitals
40. Dr Karen Dawson, Institute of Reproduction & Development, Monash
Medical Centre & Ms Catriona King, Maroondah Breast Screen
41. Ms Denise Pratt, Northern Metropolitan Community Health Service
42. Dr Julienne Grace & Dr Jan Bishop, Royal Prince Alfred Hospital
43. Mrs Marcia de Groot
44. Ms Karen Shepherd, South Australian Breast X-Ray Service
45. Ms Helen Nicol
46. Ms Vanessa Lambert
47. Ms Katherine Horne
48. Ms Anne Fletcher, Breast Care Consultant
49. Dr John McCaffrey, Queensland Cancer Fund
50. Dr Andrew Scott
51. Dr Patrick Cregan
52. Dr Paul Harnett, Westmead Hospital
53. Dr David Goldstein, Liverpool Health Service, Cancer Therapy Centre
54. Dr Dorothy Dashwood, Australian Medical Association
55. Division of Oncology, Royal Brisbane Hospital
56. Dr Michael Adam, Postgraduate Education & Peer Review Office, Royal
Adelaide Hospital
57. Dr S Archer, Multidisciplinary Breast Service, Royal Perth Hospital
58. Ms Ellie Rosenfeld, Community Medicine, University of Adelaide
59. Dr Barbara Jones, Preventive & Community Medicine Committee,The Royal
Australian College of General Practitioners
60. Dr Elizabeth Hindmarsh, RACGP Task Force, Women’s Health,The Royal
Australian College of General Practitioners
61. Dr Jim Aylward
62. Ms Pauline Chiarelli, Consultant Physiotherapist, Women’s Health and
Continence Adviser
63. Mrs Shirley Paull
64. Dr Geoffrey Ward, Adelaide Radiotherapy Centre
65. Ms Miriam Stein, Clinical Psychologist,The University of Western Australia,
Department of Psychiatry and Behavioural Science
66. Ms Sue Lockwood
67. Ms Suzanne Steginga, Queensland Cancer Fund
68. Ms Jenn Scott, School of Applied Psychology, Griffith University
69. Mrs Yvonne George
70. Mrs Joan Esplan, Box Hill Cancer Support Group
71. Ms Susan Fitzpatrick, Victorian Cooperative Oncology Group, Anti Cancer
Council
72. Mr David Hill, Centre for Behavioural Research in Cancer, Anti Cancer
Council of Victoria
73. Ms Robyn Julian
74. Clinicians of the Flinders Medical Centre, Breast Cancer Clinic
75. Mr Howard Smith, ICI Pharmaceuticals, ICI Australia Operations Pty Ltd
76. Mr Colin MacLeod, The Royal College of Pathologists of Australasia
77. Mrs Carol Bishop, Cancer Foundation of Western Australia, Breast Cancer
Support Service
78. Ms Kate Harman, Australian Physiotherapy Association
79. Ms Melba Mensch
80. Ms Elizabeth Percival, Royal College of Nursing, Australia
81. Ms Robin Gregory
82. Ms Janine Sargeant, Australian Association of Private Radiation Oncology
Practices
APPENDIX B: REVISION OF THE FIRST
EDITION (1995) AND
PRODUCTION OF THE SECOND
EDITION (2001)
In keeping with NHMRC recommendations, the guidelines have been reviewed

and updated to provide a new edition for 2001 onwards.
The steps taken in reviewing the guidelines are described below.
THE REVISION TEAM
A multidisciplinary sub-group of the first edition Working Party was established to

undertake a detailed review of the guidelines. The sub-group was chaired by
Emeritus Professor Tom Reeve, and included Associate Professor Alan Coates, Mr
Colin Furnival, Professor Allan Langlands (member until April 2000) and Ms Jayne
Ross.This group met on a number of occasions to develop directions, consider
specific issues and rewrite sections as required.
The Revision Team sought comment and collected reviews of the evidence as
detailed below. These were then reviewed and incorporated into the revised
guidelines.
Update of the evidence: overview

A review of the scientific findings on which the original guidelines were based
was completed by the Cochrane Review Group in Breast Cancer.The update was
conducted in December 1996 and repeated in December 1997. The accuracy of
the statements in the guidelines, the supporting references and the levels of
evidence were reviewed. This review included consideration of the new
overviews published by the Early Breast Cancer Trialists Collaborative Group
since the release of the first edition, addressing ovarian ablation, tamoxifen and
poly-chemotherapy.297-299
Specific areas
The Revision Group identified a number of areas where a special review was
required and requested individuals to provide these reviews as shown:
• Incidence and survival figures (Dr Anne Kricker)
• Genetics (Associate Professor John Hopper)
• Alternative and complementary therapies (amended with chapter from
draft the iSource National Breast Cancer Centre’s Clinical practice
guidelines on the management of advanced breast cancer, 2001)
• Pathology (Dr Michael Bilous)
• DCIS and LCIS (Dr Michael Bilous, Dr Geoff Delaney, Associate Professor
John Boyages, Dr Stephen Cahill)
• Breast conserving surgery with mastectomy (Mr Colin Furnival, Mr Donald
Marshall)
• Axillary dissection and lymphoedema (Professor Alan Rodger, Mr Colin
Furnival, Dr Sue Pendlebury, Mr Owen Ung)
• Postmastectomy radiotherapy (Professor Alan Rodger)
• Adjuvant therapy (Dr Ray Snyder, Professor Michael Green, Professor Alan
Coates)
Individuals were required to provide critical appraisal of key papers that had
been published since the first edition of the guidelines.These findings were
incorporated into the guidelines. Draft reviews were then sent to the working
party for consideration and final interpretation of evidence, and formulation of
recommendations was reached through discussion. In addition, the NHRMC
public consultation process provided a means of external review of the updated
chapters.
Levels of evidence
The Working Group decided that it was important to give a clear indication in the
guidelines as to the strength of the evidence for guidelines and key statements,
and to provide references where appropriate.
The levels of evidence and associated guidelines are presented in tabular form
throughout the text. The evidence cited in the guidelines has been classified as
accurately as possibly into four levels, as follows:
Level I Evidence is obtained from a systematic review of all relevant
randomised controlled trials.
Level II Evidence is obtained from at least one properly designed randomised
controlled trial.
Level III Evidence is obtained from well-designed controlled trials without
randomisation; OR from well-designed cohort or case-control analytic
studies, preferably from more than one centre or research group; OR
from multiple time series with or without the intervention.
Level IV This represents the opinions of respected authorities based on
clinical experience, descriptive studies or reports of expert
committees.
This rating system is recommended by the Quality of Care and Health Outcomes
Committee (QCHOC) and has been adapted from the system developed by the
US Preventive Services Task Force.2
The amount and strength of supporting evidence available for particular topics
varies, partly reflecting the fact that research has tended to focus on some issues
more than others. Since clinical decisions must often be made in the absence of
published evidence, a number of recommendations are based on Level III and IV
evidence. All recommendations were informed by the considered opinion of
clinical experts and were considered to be best practice. The processes used in
developing these guidelines were designed to ensure that, as well as being based
on the best available evidence, the recommendations reflect a consensus view of
early breast cancer treatment in Australia.
R E V I E W S O F E V I D E N C E A N D R E C O M M E N DAT I O N S
D E V E L O P E D B Y T H E I S O U R C E N AT I O N A L B R E A S T
C A N C E R C E N T R E A N D OT H E R G RO U P S
Since the publication of the first edition, the iSource National Breast Cancer
Centre (the Centre) and others have produced a number of reviews of specific
issues. While many of these issues were addressed in the first edition, there have
been additional evidence reviews and reports on areas concerning the
management of women with early breast cancer. Many of these were accessed for
the revision of these guidelines and are shown in the reference section of this
document.These include:
• The prognosis and management of women with ductal carcinoma in situ of
the breast. A review by Ghersi D and Simes J, NHMRC National Breast
Cancer Centre 1998
• Psychosocial clinical practice guidelines: providing information, support
and counselling for women with breast cancer, NHMRC National Breast
Cancer Centre 2000
• Report of the effectiveness of post-mastectomy radiotherapy and risk
factors for local recurrence in early breast cancer, Radiation Oncology
Advisory Group of the National Breast Cancer Centre and the Faculty of
Radiation Oncology of the Royal Australian and New Zealand College of
Radiologists in association with Ghersi D and Simes J (NHMRC Clinical
Trials Centre), in Radiotherapy and Breast Cancer, NHMRC National Breast
Cancer Centre 1999
• Lymphoedema: prevalence, risk factors and management: a review of
research, by Collete Browning and Associates, NHMRC National Breast
Cancer Centre 1997
• Review of high-dose chemotherapy as a treatment strategy for breast
cancer, Talbot S, Basser R, Boyle F, Gallelari M, Rolfe F, iSource National Breast
Cancer Centre, (in preparation)
C O N S U LTAT I O N A N D F E E D B AC K
Issues raised by major stakeholders were taken into account as described. First,
the guidelines were submitted to the NHMRC who oversaw the first and second
public consultation processes. A number of submissions were received from
experts, representatives of professional colleges and consumer representatives.
These were reviewed and considered by a sub-group of the Working Party
(including frontline clinicians, experts and consumers who have considered the
clinical relevance and validity of the evidence and decided on its implications for
practice) and modifications or inclusions were made if deemed to reflect best
practice and the available evidence. After revision, the final drafts were approved
by the sub-group. A consensus-building process was used to achieve agreement
on the resulting recommendations.
Early breast cancer guidelines sub-group

This multidisciplinary group reviewed drafts of the guidelines and was comprised of:
Emeritus Professor Tom Reeve (Australian Cancer Network), Chair
Dr Roger Allison (Radiation oncologist)
Professor Bruce Barraclough (Surgeon)
Professor Alan Coates (The Cancer Council, Australia)
Ms Mary Draper (Department of Health, Victoria)
Mr Colin Furnival (Surgeon)
Mr Anthony Green (Surgeon)
Associate Professor Michael Green (Medical oncologist)
Ms Vanessa Lambert (Consumer representative)
Professor Allan Langlands (Radiation oncologist—member until April 2000)
Ms Jayne Ross (NSW cervical screening program)
Dr Raymond Snyder (Medical oncologist)
Dr Jane Turner (Psychiatrist)
Consumers have been involved in all stages of guideline development. Consumers
are permanent members of the Early Breast Cancer Working Group, which has
overseen the development of the guidelines. Consumers unconnected to the
iSource National Breast Cancer Centre were also able to respond to the NHMRC
call for submissions on the guideline.
Feedback on the first edition of the guidelines was sought at the end of 1997 and
the beginning of 1998 from a broad range of agencies involved in breast cancer
control. The organisations consulted included:
Original Working Party (see Appendix A)
Cancer organisations
ACT Cancer Society
Anti-Cancer Council of Victoria
Australian Cancer Network
Breast Cancer Action Group of Victoria
Cancer Council of NT
Cancer Foundation of WA
Counselling and support services from each state and territory cancer
organisation (Breast Cancer Support Service and Cancer Information Service)
Medical Oncology Group
NSW Breast Cancer Institute
NSW Cancer Council
Queensland Cancer Fund
iSource National Breast Cancer Centre representatives from the

professional colleges
Royal Australian College of General Practitioners
Royal College of Pathologists of Australasia
Royal Australasian College of Radiologists
Royal Australasian College of Surgeons
Royal College of Nursing, Australia
iSource National Breast Cancer Centre’s Consumer Advisory Group

Other selected individuals from the following disciplines
Reconstructive surgery
Medical oncology
Consumers
Radiation oncology
Surgery
Psychiatry
General practice
Epidemiology
C O N T R I B U TO R S TO T H E R E V I S I O N O F T H E C L I N I C A L
P R AC T I C E G U I D E L I N E S F O R T H E M A N A G E M E N T O F E A R LY
BREAST C ANCER
Comments and contributions were also received from the following individuals
and groups:
Dr Roger Allison Radiation oncologist
Professor Bruce Barraclough Surgeon
Ms Heather Beanland Consumer
Dr Michael Bilous Pathologist
Ms Carol Bishop Coordinator, Breast Cancer Support
Service
Associate Professor John Boyages Radiation oncologist
Dr Fran Boyle Medical Oncologist
Dr Robert Broadbent Psychiatrist
Dr Colin Bull Radiation oncologist
Ms Julie Burdis Consumer representative
Ms Louise Burton Manager Supportive Care, NSW Cancer
Council
Dr Stephen Cahill Radiologist
Professor Alan Coates Medical oncologist
Dr Geoffrey Delaney Radiation oncologist
Ms Mary Draper Consumer representative
Professor Stewart Dunn Psychologist
Professor Ian Fraser Department of Obstetrics and
Gynaecology, University of Sydney
Dr Robert French Surgeon
Mr Colin Furnival General surgeon
Ms Davina Ghersi Researcher
Mr Tony Green Surgeon; expert on remote/rural access
issues
Dr Michael Green Medical oncologist
Associate Professor John Hopper Genetic epidemiologist
Mrs Norma Hudson Consumer representative
Professor David Ingram Surgeon
Mrs May Jackson Consumer representative
Mr. Jim Kollias Surgeon
Professor Allan Langlands Radiation oncologist (retired)
Ms Penny La Sette Consumer representative
Ms Liz Libregts Consumer representative
Mr Peter Malycha Surgeon
Professor Donald Marshall Plastic and reconstructive surgeon
Professor John McCaffrey Surgeon
Miss Olive McMahon Consumer representative
Mr Peter Michelson Executive officer, ACT Cancer Society
Ms Sandra Nicoll Consumer representative
Mrs Marcia O’Keefe Consumer representative,
(Deceased October 1997)
Ms Elizabeth Percival Nurse
Professor Sally Redman Chief Executive Officer,
Ms Beverly Rees Nurse counsellor
Emeritus Professor Tom Reeve Surgeon
Professor Alan Rodger Radiation oncologist
Dr Angela Rutherford General practitioner
Professor Kerstin Sandelin Surgeon
Associate Professor John Simes Clinical epidemiologist
Dr Raymond Snyder Medical oncologist
Dr Martin Stockler Medical oncologist; Co-Director of
Cancer Trials, NHMRC Clinical Trials
Centre
Mrs Lyn Swinburne Consumer representative
Ms Mavis Tassicker Consumer representative
Ms Susan Tulley Consumer representative
Dr Jane Turner Psychiatrist
Mrs Joan Van Every Consumer representative
Ms Ann Weedon State Coordinator, Breast Cancer
Support Service, NSW Cancer Council
Dr Helen Zorbas Clinical Director, iSource National
Breast Cancer Centre
iSource National Breast Cancer Centre Secretariat

Dr Karen Luxford (Evidence-based Medicine Manager)
Ms Elizabeth McInnes (Guidelines Co-ordinator)
Dr Fiona Rolfe (Project Officer)
LIST OF SUBMISSIONS RECEIVED FOR THE SECOND

E D I T I O N F I R S T S TAG E P U B L I C C O N S U LTAT I O N ( 1 9 9 9 )
1 Dr Patrick Borgen MD Director

Breast Cancer Disease Management
Team
Chief Breast Service Department of
Surgery
Memorial Sloan-Kettering Cancer
Center
New York
USA
2 Dr Tony Green Chairman
Divisional Group of Rural Surgeons
Specialist Medical Centre
207 Lake Street
CAIRNS QLD 4870
3 Professor David W Kissane Director
Centre for Palliative Care
University of Melbourne
104 Studley Park Road
KEW VIC 3101
4 Mavis Tassicker 14 Belford Avenue
EAST KEW VIC 3102
5 Geoff Delaney Radiation Oncologist
Liverpool Health Service Cancer
Therapy Centre
Locked Bag 7103
LIVERPOOL NSW 2871
6 Shirley Bowen Consumer
7 Dr MJ Turner Senior Lecturer in Psychiatry
The University of Queensland Mental
Health Centre,
K Floor, Royal Brisbane Hospital
HERSTON QLD 4029
8 Professor Allan Langlands Consultant Oncologist
5 York Street
OATLANDS NSW 2117
9 Ms Michele Kosky Executive Director
Health Consumers’ Council
GPO BOX C134
PERTH WA 6001
10 Mrs Norma Hudson NBCC Consumer Advisory Group
11 Mark Street
BURNIE TAS 7320
11 Ms Sylvia Hobbs 9 Thompson Street
WAVERLEY NSW 2024
12 Ms Karen Finch Chairperson
NT Breast Cancer Voice
GPO Box 4822
DARWIN NT 0801
13 Mr Maxwell Coleman Surgeon
438 Victoria Street
DARLINGURST NSW 2010
14 Mr Neil Wetzig Chairman, Breast Section
Suite 75, Level 3, Wesley Medical Centre
Sandford Jackson Building
30 Chasely Street
AUCHENFLOWER QLD 4066
15 Ms Marilyn Beaumont Director
Women’s Health Victoria
Queen Victoria Women’s Centre
GPO Box 1160K
MELBOURNE VIC 3001
16 Dr Debra Graves Chief Executive Officer
The Royal College of Pathologists of
Australasia
Durham Hall
207 Albion Street
SURRY HILLS NSW 2010
17 Dr Ian Gough General Surgeon, Clinical Professor
Wesley Medical Centre
40 Chasely Street
18 Dr Joseph Wong President
Australian and New Zealand Society of
Nuclear Medicine Inc
Nuclear Medicine
Royal Brisbane Hospital
HERSTON QLD 4029
19 Dr Liz Kenny Dean
The Royal Australian and New Zealand
College of Radiologists
Faculty of Radiation Oncology
Level 9, 51 Druitt Street
SYDNEY NSW 2000
20 Ms Joan Van Every PO Box 8007
PORT MACQUARIE NSW 2444
21 Professor Alan Rodger Director of Radiation Oncolgy
The William Buckland Radiotherapy
Centre
The Alfred Commercial Road
PRAHRAN VIC 3181
22 Dr Martin Borg Senior Consultant
Radiation Oncology
Royal Adelaide Hospital
North Terrace
ADELAIDE SA 5000
23 Dr Paul Thomas Area Director
Division of Nuclear Medicine
Hunter Health Imaging Service
Royal Newcastle Hospital
PO Box 664J
NEWCASTLE NSW 2300
24 Mr John Collins Specialist Breast and General Surgeon
Suite 32, Private Medical Centre
PARKVILLE VIC 3052
25 Mr James Kollias Surgeon
Breast, Endocrine and Surgical
Oncology Unit
Royal Adelaide Hospital North Terrace
ADELAIDE SA 5000
26 Dr Stephen Della-Fiorentina Staff Specialist
Department of Medical Onlcology and
Palliative Care
Locked Bag 7103
LIVERPOOL BX NSW 1871
27 Ms Patsy Yates Faculty of Health Queensland
University of Technology
Victoria Park Road
KELVIN GROVE QLD 4059
28 Ms Olive McMahon 48 Victoria Avenue
CHELMER QLD 4068
29 Professor John McCaffrey Chairman
Medical & Scientific Advisory
Committee
Queensland Cancer Fund
PO Box 201
SPRING HILL QLD 4004
30 Ms Elizabeth Percival Executive Director
Royal College of Nursing
PO Box 219
DEAKIN WEST ACT 2600
31 Ms Elizabeth Libregts Consumer Advisor
for SA
32 Dr Peter Willsher Consultant General Surgeon
Chairperson, Multidisciplinary Breast
Service
Royal Perth Hospital
GPO Box X2213
PERTH WA 6001
33 Mr John Collins Specialist Breast and General Surgeon
Royal Melbourne Hospital
PARKVILLE VIC 3052
34 Dr Graeme Morgan Radiation Oncologist
Department of Radiation Oncology
St Vincent’s Hospital Sydney Ltd
Victoria Street
DARLINGHURST NSW 2010
35 Dr Roslyn Drummond Head, Breast Unit
Division of Radiation Oncology
Peter MacCallum Cancer Institute
Locked Bag 1
A’Beckett Street
MELBOURNE VIC 3002
36 Dr Geoffrey Bower President
Australian and New Zealand Association
of Physcians in Nuclear Medicine
C/- Secretariat
PO Box 73
BALMAIN NSW 2041
37 Dr John Boyages NSW Breast Cancer Institute
PO Box 143
WESTMEAD NSW 2145
38 Dr Sue Whicker Royal Australian College of General
Practitioners
52 Parramatta Road
FOREST LODGE NSW 2037
39 Dr Raymond Snyder Department of Oncology
St Vincent’s Hospital
FITZROY VIC 3065
40 Cecily Metcalf Royal Perth Hospital
Email: cecimetc@rph.health.wa.gov.au
41 Ms Sue Lockwood Breast Cancer Action Group
PO Box 281
FAIRFIELD VIC 3078
42 Dr Peter Malycha Surgeon
333 South Terrace
ADELAIDE SA 5000
43 Dr V Ahern The Department of Radiation Oncology
Westmead Hospital
WESTMEAD NSW 2145
LIST OF SUBMISSIONS RECEIVED FOR THE SECOND
EDITION SECOND STAGE PUBLIC CONSULTATION (2000)
1 Dr Sean Bydder Registrar

Sir Charles Gardiner Hospital
PERTH WA 6009
2 Ms Michele Kosky Director
Health Consumers’ Council
GPO Box C134
PERTH WA 6839
3 Ms Marilyn Beaumont Director
Women’s Health Victoria
GPO Box 1160K
MELBOURNE VIC 3001
4 Ms Liz Libregts Consumer Advocate
ADELAIDE SA
5 Ms Olive McMahon 48 Victoria Avenue
CHELMER QLD 4068
6 Ms Norma Hudson Consumer Adviser/Advocate
11 Mark Street
BURNIE TAS 7320
7 Dr Verity Ahern Staff Specialist
Radiation Oncology
Westmead Hospital
WESTMEAD NSW 2145
8 Ms Sally Crossing Chair
Breast Cancer Action NSW
GREENWICH NSW 2065
9 Dr Debra Graves Chief Executive Officer
Royal College of Pathologists of
Australasia
207 Albion Street
SURRY HILLS NSW 2010
10 Dr Prudence Francis Peter MacCallum Cancer Institute
EAST MELBOURNE VIC 2002
11 Dr Martin Borg Senior Consultant, Radiation Oncology
Royal Adelaide Hospital Cancer Centre
ADELAIDE SA 5000
12 Mr Neil Wetzig Chairman, Section of Breast Surgery
30 Chaseley Street
13 Professor Alan Rodger Director of Radiation Oncology
William Buckland Radiotherapy Centre
The Alfred
PRAHRAN VIC 3181
14 Professor Ian Frazer Royal Australian and New Zealand
College of Obstetricians and
Gynaecologists
C/- University of Sydney
UNIVERSITY OF SYDNEY NSW 2006
15 Ms Rosemary Bryant Executive Director
Royal College of Nursing
PO Box 219
DEAKIN ACT 2600
16 Mr Peter Malycha Surgeon
333 South Terrace
ADELAIDE SA 5000
17 Dr Will Cairns President
Australian and New Zealand Society of
Palliative Medicine Inc.
C/- Townsville General Hospital
TOWNSVILLE QLD 4810
18 Dr Susan Pendlebury Staff Specialist
Royal Prince Alfred Hospital
CAMPERDOWN NSW 2050
19 Ms Jo Gniel Product Manager—Oncology
AstraZeneca
Alma Road
NORTH RYDE NSW 2113
20 Dr John Sparrow President RACMA
21 Dr RF Broadbent Executive Director
Royal Australian and New Zealand
College of Psychiatrists
309 Latrobe Street
MELBOURNE VIC 3000
22 AM Donnelly and School of Medicine
Professor Peter K Donnelly James Cook University
TOWNSVILLE QLD 4811
23 Ms Penny La Sette Consumer
PO Box 2651
DARWIN NT 0801
24 Ms Mary-Louise Whittet Project Manager
Janssen-Cilag
Locked Bag 2070
NORTH RYDE NSW 1670
25 Ms Lyn Swinburne Breast Cancer Network of Australia
PO Box 4082
AUBURN SOUTH VIC 3122
26 Dr Elizabeth Hindmarsh Royal Australian College of General
Practitioners
1 Palmerston Crescent
SOUTH MELBOURNE VIC 3205
27 Professor Allan Langlands Consultant Oncologist
5 York Street
OATLANDS NSW 2117
28 Dr Martin Stockler Sydney Cancer Centre
Royal Prince Alfred Hospital
CAMPERDOWN NSW 2050
29 Dr A Green Specialist Medical Centre
47 Jack Street
ATHERTON QLD 4883
30 Ms Jayne Ross Manager
NSW Cervical Screening Program
Westmead Hospital
WESTMEAD NSW 2145
31 Dr Helen Zorbas Clinical Director
SYDNEY NSW
I M P L E M E N TAT I O N A N D D I S S E M I N AT I O N O F T H E
GUIDELINES
The Centre will be responsible for disseminating, implementing, evaluating and

updating the revised guidelines.The implementation plan has been developed on
the basis of experience obtained through the implementation of the first edition
of the guidelines.
An initial print run of the guidelines will be disseminated to relevant professional
groups free of charge. Copies will also be made available to allied health
organisations, state and territory health authorities, breast cancer treatment
centres, consumer and patient groups, professional colleges and associations,
public policy makers, health economists and professional journals.
To assist electronic dissemination, the Centre will include these guidelines on the
it’s web page, enabling Internet access. The availability of the guidelines will be
advertised through the Centre’s newsletters, published frequently throughout the
year. The guidelines will also be distributed to professional colleges across
Australia.
Lastly, the guidelines will be promoted through national seminar series,
presentations at relevant professional meetings and conferences and submissions
to professional journals.
C O N S I D E R AT I O N O F L O C A L C O N D I T I O N A L A N D
RESOURCE CONSTRAINTS
Implementation of the guidelines will, in some cases, depend on the availability of

expertise and resources. Unfortunately, little specific evidence is available
concerning the range of local treatment options available for remote or rural
women with early breast cancer, although these services are known to be often
limited.
To assist with such issues, the Centre has been involved in the preparation of
guideline implementation kits to help address issues of local variability, and in
establishing pilot projects for electronically linking remotely located clinicians
into a network of expertise. Ideally, such a network is multidisciplinary in nature,
offering a range of expertise and assistance as well as continuity of care for
management of the disease. Clinicians and other carers from non-urban areas are
also encouraged to interact with multidisciplinary teams in the larger cities.
Other projects aimed at alleviating rural and remote isolation have included the
establishment of a Rural Surgeons Fellowship Scheme.
The guidelines have been framed in a manner that is flexible and mindful of
variations in local conditions and resource considerations. Some of the
recommendations may be difficult to implement, particularly the psychosocial
recommendations—for instance, the provision of interventions which require a
psychiatrist or clinical psychologist. However, many of these recommendations do
not require additional infrastructure, and rather call for changes in style and
approaches to the provision of information. The Centre is currently promoting
evidence-based communication skills training at a national level, and has initiated
a number of projects to explore what is required by specific treatment centres to
meet needs and develop resources (such as specialist breast nurses) in diverse
settings.
Throughout the text, reference is made to economic and cost/benefit issues.
However, there is a lack of primary research on these areas. The resources
required for additional studies to identify and test a range of economic
evaluations (cost-effectiveness and cost-utility analyses) and cost comparisons of
interventions in all possible service settings is quite significant and would
constitute a major research undertaking of several years duration. This is beyond
the scope of Centre’s resources. In Chapter 9, it is recommended that Australian
cost data are collected to allow for comprehensive analysis of the costs of
treatment options, and also that research is conducted appraising the impact of
treatment options on quality of life.
However, the Centre has commissioned two reports which have examined costs
in relation to breast cancer management. The first259 provides estimates of the out-
of-pocket expenses incurred by women in Australia in obtaining breast cancer
screening, diagnosis and treatment services outside the BreastScreen Australia
Program, based on data pertaining to the period 1995–1997. In- and out-of-
hospital medical service costs were estimated, and costs of adjuvant radiotherapy
and chemotherapy under different scenarios are presented.259 This report
emphasises that, in the Australian health care system, a woman can gain virtually
complete financial protection against the cost of medical, hospital and support
services by opting to be treated as a public outpatient or a public inpatient in a
public hospital. Further details of cost breakdowns can be found in the report.259
A second study described the average costs of diagnostic management at a
Sydney-based breast clinic in the context of clinical practice guidelines for the
diagnosis of women presenting with symptoms which may be caused by breast
cancer.383 For this clinic the average costs of diagnostic management and the
average cost of diagnostic procedures are detailed in the report of the study.383 It
was concluded that the cost of diagnosis for women with breast problems cannot
be compartmentalised into a set of procedural based events, and that overall
clinical management plays an important role in the process of diagnosis. Although
this study achieved a first step in estimating the marginal cost-effectiveness of
implementing evidence-based guidelines for the management of women
presenting with breast symptoms, it is not generalisable to the rest of the state or
the country.383
For discussion of the economics and costs and benefits of different treatments,
readers are referred to the chapters on surgery, radiotherapy, systemic adjuvant
therapy and follow-up.
E VA L U AT I O N A N D U P DAT I N G
An essential part of the guideline development and implementation process is an

evaluation of their effectiveness. An evaluation strategy will be drafted at the
implementation stage and will include the collection of data to determine the
impact of the guidelines on clinician behaviour and patient health outcomes.
The Centre has already undertaken key steps to facilitate this process. Baseline
data have already been collected on women’s perceptions of care through the
Centre’s National Consumer Survey (NCS). The NCS was based on a
representative national sample of women treated for breast cancer in the
preceding 12 months.This information will assist the development of an
implementation strategy.
The guidelines reflect the best available knowledge at the time of their
publication. However, they will require regular revision in order to maintain
validity as new evidence emerges from systematic reviews. The Centre proposes
to investigate the most cost-effective way of achieving this. Collaboration
between the Centre’s Treatment team and the Early Breast Cancer Working Group
(which meets quarterly) provides an established mechanism to review advances
in the field and implications for revising the guidelines.
In addition, the Centre’s experience with the evaluation and revision of the early
breast cancer guidelines and with the Cochrane Review Group in Breast Cancer
will assist with the guideline review process. The Centre will continue to foster
close links with the Australasian Cochrane Centre and relevant international
guideline bodies in order to facilitate the updating of the guidelines.
APPENDIX C: TNM CLINICAL
C L A S S I F I C AT I O N
The most widely used classification for breast carcinomas is the TNM
classification.1 T, N and M categories (tumour, nodes and metastases respectively)
are assessed by the combination of physical examination and imaging such as
mammography.
T—Primary tumour categories

TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
Tis Carcinoma in situ: intraductal carcinoma, or lobular carcinoma in
situ, or Paget disease of the nipple with no tumour
Note: Paget disease associated with a tumour is classified according to
the size of the tumour.
T1 Tumour 2 cm or less in greatest dimension
T1mic — Microinvasion 0.1 cm or less in greatest dimension.
T1a — More than 0.1 cm but not more than 0.5 cm in greatest
dimension
T1b — More than 0.5 cm but not more than 1 cm in greatest
dimension
T1c — More than 1 cm but not more than 2 cm in greatest dimension
T2 Tumour more than 2 cm but not more than 5 cm in greatest dimension
T3 Tumour more than 5 cm in greatest dimension
T4 Tumour of any size with direct extension to chest wall or skin
Note: Chest wall includes ribs, intercostal muscles and serratus anterior
muscle but not pectoral muscle.
T4a — Extension to chest wall
T4b — Oedema (including peau d’orange), or ulceration of the skin of
the breast, or satellite skin nodules confined to the same breast
T4c — Both 4a and 4b above
T4d — Inflammatory carcinoma
N—Node categories
NX Regional lymph nodes cannot be assessed (eg because previously removed)
N0 No regional lymph nodes metastasis
N1 Metastasis to movable ipsilateral axillary lymph node/s
N2 Metastasis to ipsilateral axillary lymph node/s fixed to one another or to
other structures
N3 Metastasis to ipsilateral internal mammary lymph node/s
M—Metastases categories
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastases (includes metastasis to supraclavicular lymph nodes)
Stage grouping
Stage T classn N classn M classn

Stage 0 Tis N0 M0
1
Stage I T1 N0 M0
Stage IIA T0 N1 M0
T11 N12 M0
T2 N0 M0
Stage IIB T2 N1 M0
T3 N0 M0
Stage IIIA T0 N2 M0
1
T1 N2 M0
T2 N2 M0
T3 N1, N2 M0
Stage IIIB T4 Any N M0
Any T N3 M0
Stage IV Any T Any N M1
Note:
1. T1 includes T1mic
2. The prognosis of patients with pN1a is similar to that of patients with pN0.
Note that these are clinical categories. It is also possible to use the pTNM system of classification based
on pathological examination of the tumour and axillary lymph nodes.
A P P E N D I X D : R A C O G B U L L E T I N VO L 1 0 , N O 1 ,
M AY 1 9 9 6
F RO M T H E W O R K I N G P A RT Y O N TA M OX I F E N A N D T H E
ENDOMETRIUM*
Tamoxifen is the endocrine treatment of choice for selected patients with breast
cancer, and is presently being trialed in Australia and elsewhere for its
prophylactic value in healthy women at increased risk of developing breast
cancer. Although tamoxifen functions as an anti-estrogen, it also has weak and
variable estrogenic effects.
Because of its weak estrogenic activity, tamoxifen produces a number of side
effects on the female genital tract.These may include:
• Estrogen-like changes in the vaginal epithelium of some patients.
• Stimulation of endometriosis, with worsening of symptoms in some
patients.There has been one case report of an endometroid carcinoma
arising from an ovarian endometriotic focus.
• Stimulation of the growth of benign fibroids.
• An increased incidence of benign endometrial polyps.
• An increase of benign endometrial proliferation. In post-menopausal
women, it would seem that the incidence of atrophic endometrium is
about 36 per cent in women on tamoxifen, compared to 73 per cent in
control patients, while the incidence of proliferate endometrium is about
20 per cent (10 per cent in controls), endometrial polyps 11 per cent
(3 per cent in controls) and endometrial hyperplasia 6 per cent (0.6 per
cent in controls).
• A two- to three-fold increase in incidence of endometrial carcinoma.There
have been about 250 reported cases of endometrial carcinoma in
tamoxifen-treated patients and only one case was in a pre-menopausal
woman. About 80 per cent of these cancers were stage 1 and either Grade 1
or 2, which is comparable to the situation in non tamoxifen-treated women.
The risk increases with increasing duration of use, being about 3 fold for
patients on tamoxifen longer than 5 years.
• There have been isolated reports of uterine sarcomas in women on
tamoxifen and a single case of fallopian tube cancer.
Opinions vary widely in the literature and amongst clinicians on the surveillance
of patients on tamoxifen therapy who have an intact uterus. Trans-vaginal
ultrasonography is relatively non-invasive and will detect a relatively high
* Reproduced with permission from the RACOG (Royal Australian College of Obstetricians and
Gynaecologists) Gynaecological Oncology Subspecialty Committee.
proportion of abnormalities. Biopsy of these lesions has produced a wide range of
mainly benign pathologies and demonstrated that many of the ultrasonic
abnormalities in fact appear to be located in the myometrium. Outpatient
hysteroscopy and/or endometrial biopsy are more invasive and less well tolerated
in post-menopausal women. Withdrawal bleeding following administration of
progestogens is another possible method of screening asymptomatic women for
endometrial proliferation. The specificity, sensitivity and cost-effectiveness of
these various methods of monitoring are presently unknown.
Because the incidence of endometrial carcinoma is very low (2–3/1000 women
per year) during or after tamoxifen therapy, and because there is no convincing
evidence that the stage or grade of these tumours differs from that seen in the
general population, the working party felt there were no data to support active
investigation of asymptomatic women at the present time.
The working party resolved that:
• All women taking tamoxifen should be informed of its potential side effects,
including specifically two to three fold increased incidence of endometrial
cancer.They should be warned of the possible symptoms of endometrial
cancer, including inter-menstrual or post-menopausal bleeding, abnormal
vaginal discharge or pelvic pain.
• All patients on tamoxifen should have a baseline pelvic examination. This
should include a speculum examination to determine the presence or
absence of a cervix and to take a pap smear (if appropriate), and a bi-
manual examination to evaluate the size of the uterus and the adnexae.
• Any woman complaining of symptoms should be actively investigated
immediately.
• If an individual patient expresses particular concern about the possibility of
developing endometrial cancer, or is felt to be at additional risk because of
a family history of breast, ovarian, endometrial or bowel cancer, the patient
should be referred to a gynaecologist and offered investigation at the
discretion of the gynaecologist. A vaginal ultrasound performed by a skilled
gynaecological ultrasonographer would seem to be the least invasive and
most useful initial investigation. Ultrasonography may select out those
women with atrophic or inactive endometrium from those with possible
pathology, who may require further intervention.
• Because of the absence of data establishing the sensitivity, specificity,
clinical value and cost effectiveness of active investigation of asymptomatic
women, such research should be encouraged and supported.
These recommendations, which apply to both the therapeutic and prophylactic
use of tamoxifen, will be reviewed regularly in the light of any new evidence
which may emerge.
Members of the Working Party
Professor Neville Hacker (Convenor)
Dr Margaret Davy (In absentia)
Mr Arthur Day
Dr John Eden
Dr James Grimwade
Dr Michael Quinn
Mr Robert Rome
Dr Mandy Samson
Dr Peter Warren (In absentia)
Dr Barry Wren
Dr Tom Jobling (In absentia)
In attendance (representing the Australia-New Zealand Breast Cancer Trials

Group):
Professor Alan Coates
Professor John Forbes
A P P E N D I X E : Q U E S T I O N S YO U M AY B E A S K E D
For many women, being diagnosed with breast cancer is a great shock. Most
women know little about breast cancer and its treatment. In many cases, they
don’t even know where to start asking questions.
Following is a list of questions which women may ask about their cancer,
treatment and prognosis:
General questions
• Do you mind if I tape record this consultation?
• Do you mind if my friend/relative comes in with me?
• Why did I get breast cancer?
• What type of breast cancer have I got? Where exactly is it? Is it only in the
breast or has it spread?
• Am I hormone receptor-positive or receptor-negative? What does this
mean?
• Do I need more tests? What sort of tests? Why do I need them? What do you
expect them to show?
• With each test, what happens? What are the risks? The benefits? Is the test
conventional or experimental? Who will do it? What other options exist?
• When will the results be available?
• How certain are you that the results of these tests will be accurate?
• Are there any specialist centres for the treatment of breast cancer?
• How can I find a doctor/surgeon/oncologist/counsellor I feel comfortable
with?
• In everything you tell me about tests and treatment, how much uncertainty
is there?
• How will the cancer affect my personal and sexual relationships?
• What emotions might I experience?
Surgery
• Do I have a choice between breast conserving surgery and mastectomy?
• Exactly what is involved in each type of surgery? Exactly how much will
you remove? Will you remove the lymph nodes under my arm? Will you
remove either of my chest muscles? Where will the scar/s be and what will
they look like? Can you show me pictures?
• How will I feel after surgery? How long will I take to recover?
• Where can I go for a prosthesis? Who can help fit it?
• Can I see photographs of women who have had mastectomies,
lumpectomies, partial mastectomies and/or reconstructions?
• If I have a mastectomy, can I have breast reconstruction? Can this be done
during the same operation?
Radiotherapy
• Why do you think I should (or should not) have radiotherapy?
• If I have radiotherapy, what type of radiotherapy will I have?
• Who will do it? When? Where?
• How long will it take?
Chemotherapy
• Why do you think I should (or should not) have chemotherapy?
• If I have chemotherapy, how will it be given? For how long?
• Will the drugs make me sick? Will it make my hair fall out?
• Will I still be able to work?
Hormone therapy
• Why do you think I should (or should not) have hormone therapy?
• If I have hormone therapy, what type of hormone therapy will it be?
• Can I have a form of hormone therapy that does not induce permanent
menopause?
Deciding about treatment

• What treatment do you recommend? Why?
• What happens if I choose a different treatment? Or no treatment?
• For all these treatments, what benefits would you expect for the average
woman?
Am I the average woman?
• For all these treatments, what are the risks?
• How successful are these treatments for my type of breast cancer? Will they
cure me, or will they control the cancer? In what way will they control the
cancer? Will they mean I live longer? Will they reduce any problems the
cancer’s giving me? What will my life be like during and after treatment?
• Will there be any permanent damage? Will I still be able to have children?
Will I be able to breast feed? Will I get my menopause early? Will my sex life
be affected?
• I would like at least a week to make a decision—are you comfortable with
this?
Questions relating to treatment
• How much time will all this take? Will I have to stay in hospital?
• How long will I be away from work?
• How much will it all cost?
• Do I need to use contraception during my treatment? Will I have to wait for
a while after my treatment before I can become pregnant?
• Is there anything I need to be particularly careful about during my
treatment?
• Is there anything I can do to help during my treatment? Should I eat special
foods? How can I reduce stress?
• If I need a wig or breast prosthesis, how will I get one? Will I need special
clothing?
• Am I entitled to any benefits and services, such as subsidies for travel or
prostheses?
• What side effects can I expect? What can I do about them?
• Are there any side effects or problems I should tell you about immediately?
How do I get in touch with you to do this? What if the problem occurs out
of hours?
• How will you know if the treatment’s working? What sort of tests will you
do? How often will you do them? How long will they take to do? When will
you have the results?
Lymph nodes
• What are lymph nodes? Why are they important in breast cancer?
• Will the surgery involve removing the lymph nodes? If so, what are the
risks, side effects and complications of the operation?
• Can I prevent these complications?
• If I get them, how do I treat them?
Reconstruction
• Is reconstruction possible? What are the advantages and disadvantages of
having reconstruction?
• If I choose to have a breast reconstruction, what is the best time for it—
straight away or later?
• How would it be done? Who would do it?
• Would you have to operate on my other breast? Can you construct a nipple?
How would you do this?
• Can you show me photographs of breasts you have reconstructed?
• How long would I have to stay in hospital? How many operations would I
need?
• How long would it take me to recover? What side effects can I expect? Are
there likely to be any complications or problems?
After treatment
• What long-term effects—physical, mental, emotional, social, sexual or
anything else—may occur?
• Is there anything I should be particularly careful about after my treatment
ends? Will I need to come back for a check-up? When should I come back?
How often should I have mammograms?
• Is the cancer likely to come back? Where would it come back, if it does
come back? Will I get it in the other breast? What signs should I look out
for? What can I ignore?
Support
• Do you know of any local support groups? Where can I find out what
support services are available?
• Can I talk to a counsellor? Is there a counsellor available to talk to my
family?
• Can I talk to someone who has been in my situation and who has had
treatment similar to the treatment you are recommending for me?
• What should I tell my family? What should I tell my children?
Information
• Where can I get more information on breast cancer and its treatment?
• Who can I contact if I have more questions between now and my next
consultation with you?
• Can you show me how to examine my own breasts?
A P P E N D I X F : N AT I O N A L B R E A S T C A N C E R
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NEWSLETTERS
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newsletter which reviews recent
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iSOURCE National Breast Cancer Centre Publications Order Form
Patterns of breast cancer
Guidelines and recommendations
ICP Ascertainment and reporting of interval cancers within the BreastScreen Australia Program
RCS Current recording and registration practices for carcinoma in situ of the breast in Australasian State and
Territory cancer registries.
NPR National protocol for recording 1. size, nodal status and grade of invasive breast cancer, 2. carcinoma in
situ
Reports, research and data reviews
BC1 Breast cancer in Australian women, 1921-1994
BC2 Breast cancer in Australian women, 1982-1996
DCA Ductal carcinoma in situ (DCIS): Cancer Monitoring No 1
SAW Breast cancer survival in Australian women 1982-1994
NSW Breast cancer survival in NSW in 1973 to 1995
DCN Ductal carcinoma in situ in NSW women in 1995 to 1997
NTS Surgical management of breast cancer in Australia in 1995
WAS Trends in the incidence, surgical management and survival of breast cancer patients over 13 years in WA
1982-1994
WEBSITE ONLY Report on the 1996 breast health survey
Breast cancer: general
MAD Australia’s first national breast cancer conference for women – Making a difference: actions recommended
by women with breast cancer for the benefit of the Australian community
RR Breast cancer research in Australia: current research and future priorities
CIA Catalogue of resources on breast health and breast cancer Part 1: Australian resources (1998)
DAO Don’t ask for an opinion – ask for a scalpel: print media coverage of breast cancer in Australia in 1995
ITP Evaluation of a breast cancer information training package for the Cancer Information Service
WEBSITE ONLY Review of public materials intended for general dissemination: executive summary
Information for consumers
RAD Women and breast cancer (set of 5 radio programs on cassette) $22 each* (incl. GST)
Risk factors
BOG Advice about familial aspects of breast cancer and ovarian cancer: a guide for health professionals (card)
WEBSITE ONLY Current best advice about familial aspects of breast cancer: a guide for general practitioners (card)
PSC Psychosocial factors and the risk of developing breast cancer (review)
SPU Some public health issues in the current state of genetic testing for breast cancer in Australia
SRF Summary of risk factors for breast cancer
BCF Breast cancer and family history: what you need to know (booklet)
PMF Information for women considering preventive mastectomy because of a strong family history of cancer. NB
This booklet is intended for use primarily by breast surgeons, breast specialists, oncologists, family cancer
clinics and genetic counselling services.
WEBSITE ONLY Best advice on familial aspects of breast cancer: a guide for general practitioners. Phase 2: Evaluation
WEBSITE ONLY Diet and breast cancer (review)
WEBSITE ONLY Evaluation of best advice on familial aspects of breast cancer for general practitioners
Early detection and diagnosis
BSP Breast-self examination: a position statement from the National Breast Cancer Centre.
IBS Investigation of a new breast symptom: a guide for general practitioners. (card)
PAT Pathology reporting of breast cancer: a guide for pathologists, surgeons and radiologists. (ACN)
HP1 Screening women aged 40-49 years: a summary of the evidence for health professionals
Report, research and data reviews
BSS Breast self examination and the early detection of breast cancer: a summary of the evidence for health
professionals
BSE Effectiveness of breast self-examination: a literature review.
SYM Evidence relevant to guidelines for the investigation of breast symptoms
IBA Investigation of a new breast symptom: an audit in general practice
NAP National audit of pathology reporting of breast cancer: a summary
PSM Perceptions of screening mammography amongst women aged 40-49
AHL Prevalence, screening and management of atypical hyperplasia and lobular carcinoma in situ
DCI Prognosis and management of women with ductal carcinoma in situ of the breast: a review
MMG Review of the evidence about the value of mammographic screening in 40-49 year old women
BCB Breast changes: what you need to know (booklet)
WEBSITE ONLY New technologies in breast cancer diagnosis: information update
Corporate
AR5 Annual report 1999-2000: Achieving sustainable change
AR4 Annual report 1998-1999: Partnerships to improve breast cancer control
SD Strategic Directions June 1999 – June 2003
WEBSITE ONLY Annual report 1995-1996: Translating research into action
WEBSITE ONLY Annual report 1996-1997: Improving breast cancer control
WEBSITE ONLY Annual report 1997-1998. National directions in breast cancer control
WEBSITE ONLY Consultative report: summary and outcomes. Volume 1
WEBSITE ONLY Consultative report: reports from State/Territory workshops Volume 2
Professional
CAK Cameo-B: A model curriculum for medical students: breast cancer modules $54.95 each* (incl. GST)
LIC Legal implications of clinical practice guidelines (a recommendations paper)
MLG Medicolegal implications of clinical practice guidelines in the diagnosis and treatment of breast cancer and
legal implications of clinical practice guidelines (a recommendation paper)
Medicolegal implications of clinical practice guidelines in the diagnosis and treatment of breast cancer and
legal implications of clinical practice guidelines: an executive summary
DRV Drivetime radio with Dr John D’Arcy. Medical edition #33. Side B: Living with breast cancer: key issues in
familial aspects of breast cancer; determining risk factors and patient counselling; the management of
early breast cancer
DR2 Drivetime radio with Dr John D’Arcy. Medical edition #39. Side A: Breast cancer guidelines for the
diagnosis of symptomatic women
Medicine and the Law (MJA Article)
Treatment
CPG Clinical practice guidelines for the management of early breast cancer (NB guideline is being revised)
ADV Clinical practice guidelines for the management of advanced breast cancer
MBC Management of early breast cancer for GPs: action based on evidence. (card) (NB guideline is being
revised)
RUK Systemic adjuvant therapy for women with early breast cancer: An educational kit for health care
professionals practising in regional areas of Australia (NB due to limited numbers, the Kit is limited to
one copy per organisation)
RBC Radiotherapy and breast cancer
MAX Management of the Axilla in women with breast cancer
NRT New radiotherapy techniques
CYT Management of advanced breast cancer: systematic reviews of randomised controlled trials regarding the
use of cytotoxic chemotherapy and endocrine therapy
SWT Should women take part in clinical trials in breast cancer? The issues and some solutions
MCG A guide for women with metastatic breast cancer (booklet)
AAB All about early breast cancer (booklet) (NB: booklet is being revised)
AAC All about early breast cancer (cassette)
AAR All about early breast cancer (CD ROM) $16.50 (incl. GST)
Support
PCG Psychosocial clinical practice guidelines: providing information, support and counselling for women with
breast cancer
PRM An examination of procedures reimbursed under Medicare for breast disease and breast cancer in
Australia, 1985 to 1996
DSW Cost of diagnostic investigations for women presenting with breast symptoms, The
DCX Experience of diagnosis; information and support needs of women diagnosed with ductal carcinoma in situ
LRS Encouraging research into lymphoedema: a report on the summit held on 25 and 26 February 2000
LRR Encouraging research into lymphoedema: a register of lymphoedema research
LYM Lymphoedema: prevalence, risk factors and management: a review of research
LPD Lymphoedema prevention, diagnosis and treatment. Literature search
NCM Needs of children of mothers with advanced breast cancer
OPE Out-of-pocket expenses incurred by women for diagnosis and treatment of breast cancer in Australia
PIS Psychosocial impact of breast cancer: a summary of the literature 1986-1996
ISP Psychosocial support for breast cancer patients: a review of Interventions by specialist providers. A
summary of the literature 1976-1996
MTT Psychosocial support for breast cancer patients provided by members of the treatment team. A summary
of the literature 1976-1996
SBN Specialist breast nurses: an evidence-based model for Australian practice
SSR Strengthening support for women with breast cancer: a background paper
ETQ Supplementary report on the effects of treatment on quality of life
TPE Talking about prognosis with women who have early breast cancer: what they prefer to know and
guidelines to help explain it effectively
WEBSITE ONLY A consumer’s guide to early breast cancer
WEBSITE ONLY Breast reconstruction: a review of the research and patient and professional resources
WEBSITE ONLY Satisfaction with breast cancer care: a summary of the literature 1984-1994
WEBSITE ONLY Strengthening support for women with breast cancer: principles, outcomes and models paper
REC Breast reconstruction: your decision (video)
PTA When the woman you love has advanced breast cancer (cassette) $11 each* (incl. GST)
PTE When the woman you love has early breast cancer (cassette) $11 each* (incl. GST)
Women from indigenous and non-English speaking background
BCA Breast cancer and Aboriginal and Torres Strait Islander women
HBA Healthy breasts (Arabic booklet)
HBG Healthy breasts (Greek booklet)
HBI Healthy breasts (Italian booklet)
HBP Healthy breasts (Polish booklet)
WEBSITE ONLY Exploring cultural attitudes to breast cancer: towards the development of culturally appropriate information
resources
Flyers and posters
AAP All about early breast cancer (poster)
REF Breast reconstruction your decision (flyer)
BCG Breast changes? Take action. Ask your GP (poster)
BAL Breast changes? Take action. Ask your librarian (poster)
GPA GP actions for the patient with early breast cancer (sheet of 6 stickers)
WYP What you do after you find a change in your breast could change your life (poster)
WYB What you do after you find a change in your breast could change your life (brochure)
RAF Women and breast cancer (flyer for the radio program)
Newsletters, catalogues
BNM Breast News (quarterly). Please add my name to the mailing list
BFF Breast Fax (monthly via fax). Please add my name to the distribution list, my fax number is
below
BFE Breast Fax (monthly via e-mail). Please add my name to the distribution list, my e-mail address
is below
CLM Clinical Update (quarterly). Please add my name to the mailing list
WEBSITE ONLY Review of materials about breast health and breast cancer intended for general dissemination
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patients and an observed response rate of 33 per cent has a 95 per cent
confidence interval of 16–55%. While tumour response rate is a reasonable
endpoint for assessing the anticancer activity of a drug, it is not an adequate
surrogate for patient benefit.
Phase II trials are suitable for guiding decisions about further research, but are
not suitable for making or guiding decisions about patient management. The
literature is often confusing on this point, because phase II trials are often
reported and interpreted as if they do provide answers to questions about patient
management.385
Phase III trials are pragmatic since they are designed to answer questions about
the usefulness of treatments in patient management. Questions about patient
management tend to be comparative since they involve choices between
alternatives, that is, an experimental management versus the current standard. The
current standard may include other anticancer treatments, or may be the best
supportive care without specific anticancer therapy.
The aim of a phase III trial is to estimate the difference in outcomes associated
with a difference in treatments, sometimes referred to as the treatment effect.
Ideally, alternative treatments are compared by administering them to groups of
patients which are equivalent in all other respects. Randomised controlled phase
III trials are the best, and often only reliable, means of determining the usefulness
of treatments in patient management.
Table 8: Classification of clinical trials
Characteristic Explanatory Pragmatic
Purpose To guide research and To guide patient management
provide information about and provide information
mechanisms and specific about net effects and patient
effects of treatment benefit
Primary focus The treatment The patient
Conditions Idealised Real
Treatment Chosen to accentuate the Chosen with tolerance of the
phenomenon under study target population in mind
Controls Chosen to isolate the Chosen according to
phenomenon of interest standard practice
Assessment criteria Direct measures of biological Direct measures of patient
activity, such as tumour benefit such as survival, quality
response and host toxicity of life and functional capacity
Choice of patients Those most likely to Those most typical of the
demonstrate an effect patients to whom the results
will be applied
The contact numbers for the Australian New Zealand Breast Cancer Trials Group
(ANZBCTG) are phone: 02 4921 1896; fax: 02 4967 2351.
A P P E N D I X H : B R E A S T C A N C E R S U P P O RT
S E RV I C E S
To find out about breast cancer support groups and other local services, contact
your state or territory cancer organisations and the Cancer Information Service.
The Cancer Information Service can be contacted in any state/territory by
telephone on: 13 11 20.
• The Cancer Council ACT
159 Maribyrnong Avenue
KALEEN ACT 2617
Phone: 06 6262 2222
Fax: 06 6262 2223
Email: chl@actcancer.org
Website: www.actcancer.org.au
• Anti-Cancer Council of Victoria

Rathdowne Street
CARLTON SOUTH VIC 3053
Phone: 03 9635 5000
Fax: 03 9635 5270
Email: enquiries@accv.org.au
Website: www.accv.org.au
• Anti-Cancer Foundation of South Australia

202 Greenhill Road
EASTWOOD SA 5063
Phone: 08 8291 4111
Fax: 08 8291 4122
Email: acf@cancersa.org.au
Website: www.cancersa.org.au
• The Cancer Council Tasmania

140 Bathurst Street
HOBART TAS 7000
Phone: 03 6233 2030
Fax: 093 6233 2123
Email: Iride@courier.tas.gov.au
Website: www.cancer.org.au/tas
• Cancer Foundation of Western Australia Inc
46 Ventnor Avenue
WEST PERTH WA 6005
Phone: 089212 4333
Fax: 08 9212 4334
Email: cancerwa@cancerwa.asn.au
Website: www.cancerwa.asn.au
• The Cancer Council Northern Territory

Unit 1-3
23 Vanderlin Drive
CASUARINA NT 0810
Phone: 08 8927 4888
Fax: 08 8972 4990
Email: uvstop@cancernt.org.au
Website: www.cancercouncilnt.citysearch.com.au
• The Cancer Council, New South Wales

153 Dowling Street
WOOLLOOMOOLOO NSW 2011
Phone: 02 9334 1900
Fax: 02 9357 2676
Email: feedback@nswcc.org.au
Website: www.nswcc.org.au
• Queensland Cancer Fund

553 Gregory Terrace
FORTITUDE VALLEY QLD 4006
Phone: 07 3258 2200
Fax: 07 3257 1306
Email: qldcf@qldcancer.com.au
Website: www.qldcancer.com.au
Other breast cancer services for women
• Breast Cancer Network of Australia (BCNA)
PO Box 4082
AUBURN SOUTH VIC 3122
Phone: (03) 9805 2500
Fax: (03) 9805 2599
Email: beacon@bcna.org.au
Website: www.bcna.org.au
The BCNA produces The Beacon—a newsletter for women with breast
cancer
• Action on Breast Cancer WA

Contact: Carol Bishop
55 Monash Avenue
NEDLANDS WA 6009
Phone: (08) 9489 7312
• Tasmanian Breast Cancer Network

Contact: Pat Mathew
51 Macfie Street
DEVONPORT TAS 7310
Phone: (03) 6423 3637
• Bosom Buddies Inc

Contact: 02 6230 2881
• Breast Cancer Action Group (VlC)

PO Box 281
FAIRFIELD VIC 3078
Fax: (03) 9457 6318
• Breast Cancer Action Group (NSW)

Contact: Sally Crossing
PO Box 5016
GREENWICH NSW 2065
Phone/Fax: (02) 9436 1755
• Action for Breast Cancer South Australia

Contact: Denise Wehnert
Phone: (08) 8449 7761
• NT Breast Cancer Voice
Contact: Karen Finch
GPO Box 4822
DARWIN NT 0801
Phone: (08) 8945 6582
Lymphoedema Associations & Support Groups

These groups provide information on lymphoedema, local services and resources
and support to women with lymphoedema.
• The Australian Lymphology Association
8 Kergo Place
WANTIRNA SOUTH VIC 3152
• ACT Lymphoedema Support Group

66 Bindaga Street
ARANDA ACT 2614
Phone: (02) 6251 1294
• Darwin Lymphoedema Support Group

PO Box 4127
CASUARINA NT 0811
Phone: (08) 8927 4888
Fax: (08) 8927 4990
• Lymphoedema Support Group of NSW

79 Beechworth Road
PYMBLE NSW 2073
Phone: 02 9402 5625
• Lymphoedema Support Group of SA

PO Box 1006
KENT TOWN SA 5071
Phone: (08) 8204 4711
• Tasmanian Lymphoedema Support Group

C/- 42 Stanley Street
BELLERIVE HOBART TAS 7018
Phone: (03) 62444634
• Lymphoedema Association of Victoria
PO Box 2412
NORTH RINGWOOD VIC 3134
Phone: 1300 852 850
• Lymphoedema Association of Western Australia
C/- Crawford House
15 Bedbrook Place
SHENTON PARK WA 6008
Phone: (08) 9381 2070
Useful web sites:

Breast Cancer Network of Australia
www.bcna.org
www.nbcc.org.au
The Cancer Council Australia
www.cancer.org.au
A P P E N D I X I : R OYA L A U S T R A L A S I A N
COLLEGE OF SURGEONS
BREAST AUDIT
The Royal Australasian College of Surgeons, (RACS) Breast Audit, set up as a

collaborative venture with the iSource National Breast Cancer Centre, is now the
recommended audit instrument for breast surgeons who are members of the
Section of Breast Surgery, RACS. Use of this audit is an obligatory component of
membership of the Section.
Information can be obtained from:
Ms Sarah Tyson, Project Manager
PO Box 688
NORTH ADELAIDE SA 5006
Phone: (08) 8361 9077
Fax: (08) 8239 1244
Email: breast.audit@racs.edu.au
G L O S S A RY
Adjuvant chemotherapy/hormone therapy

The use of either chemotherapy or hormone therapy after primary
treatment either by surgery or radiotherapy, or a combination of these
(usually within six weeks) to eradicate micrometastatic cancer. A way of
having one treatment assist another.
Alopecia
Hair loss. In the context of breast cancer, usually caused by one of the
chemotherapeutic drugs. It is usually partial and short-term, and full
recovery usually occurs.
Anti-oncogene
See tumour suppressor gene or anti-oncogene.
ANZBCTG
Australian New Zealand Breast Cancer Trials Group. National clinical
trials group which conducts research on new treatments.
Anxiety
A diffuse, highly unpleasant, often vague feeling of apprehension,
accompanied by bodily sensations such as pounding heart and sweating.
There is an associated anticipation of future misfortune or danger,
external or internal.
Atypia
Histological or cytological abnormal changes in epithelial cells. See also
dysplasia.
Atypical ductal hyperplasia

Increased numbers of ductal epithelial cells which show some but not
all the features of in situ carcinoma: associated with a significant risk of
developing subsequent carcinoma in either breast.
Axilla
Fossa axillaris; armpit.
Axillary dissection
Surgical excision of the axillary contents (fat and lymph nodes) en bloc
with mastectomy or as an independent procedure. The extent of the
axillary dissection is further defined in the following way:
Level 1—excision of the axillary contents up to the inferior border of
the pectoralis minor muscle.
Level 2—excision of the axillary contents up to the superior border of
the pectoralis minor muscle.
Level 3—excision of the axillary contents up to the apex of the axilla.
Axillary sampling
An ill-defined procedure which varies from the excision of a single, low
axillary node to the excision of the lower axillary contents as in a Level
1 axillary dissection.
Biopsy
Removal of a sample of tissue or cells from the body by excision or
aspiration for microscopic examination to assist in diagnosis of a
disease.
Body image
The individual’s conception of and feelings about their body — its
overall integrity, its physical characteristics such as form, size and shape,
and its conformity to societal values and norms. Self-esteem,
psychosocial functioning and sexuality are intimately linked with body
image.
Bone scan
An investigation carried out to assess the presence or absence of
metastatic disease. The uptake of a radio-nuclide in bone is determined.
Sites of increased activity frequently represent metastatic disease.
Boost
An additional dose of radiation given to a smaller volume, usually the
local excision site, after the remainder of the breast has been irradiated.
Brachytherapy
The use of isotopes inserted into tissue to deliver radiation to a limited
volume. See also teletherapy.
BRCA1
Breast cancer gene 1. It is identified as a gene on the long arm of
chromosome 17 which is mutated or lost in 2–4 per cent of women
with breast cancer. See also familial breast cancer.
BRCA2
Breast cancer gene 2 has been identified recently on chromosome 13.
See also familial breast cancer.
Breast conserving surgery

Surgery where the breast cancer is excised together with a margin of
normal breast tissue. The whole breast is not removed.
Breast reconstruction
The creation or insertion of a breast shape or mound using surgical
techniques, after a total mastectomy.
Breast sharing
This is a method of reconstruction in which some of the opposite breast
is used to reconstruct the missing breast.
Calcification
The deposition of calcium salts in body tissues. In the breast,
calcification can be seen in normal and abnormal ducts and in
association with some carcinomas, both invasive and in situ.
Carcinoma
A malignant tumour arising from epithelial cells, which are cells lining
the external or internal surfaces of the body. Carcinomas spread by local
infiltration and may also spread to distant sites such as lung, liver, lymph
nodes and bone. See also metastasis.
Carcinoma in situ
A malignant tumour which has not yet become invasive but is confined
to the layer of cells from which it arose. A form of pre-invasive cancer.
Carcinoma NOS
Invasive ductal carcinoma not otherwise specified. Comprises 70 per
cent of all breast cancers.
Cathepsin D
A protein with proteolytic and mitogenic activity secreted by breast
cancer cells and postulated to be a marker of poor prognosis.
Centigray
1 centigray = 1 rad. This is a system used in the United Kingdom which
allows the actual numbers to remain unchanged with the move from RAD
to GRAY. For example, 4500 rads is 45 Gray or 4500 centigray.
Chemotherapy
The use of medications (drugs) to kill cancer cells, or to prevent or slow
their growth.
Chromosome
A body in the cell nucleus carrying genes. See gene.
CLE
See complete local excision.
Clinical trial
Research conducted with the patient’s permission which usually
involves a comparison of two or more treatments or diagnostic methods.
The aim is to gain better understanding of the underlying disease
process and/or methods to treat it. A clinical trial is conducted with
rigorous scientific method for determining the effectiveness of a
proposed treatment.
Combined modality treatment

The integration of two or more forms of treatment to combat the cancer.
For example: radiation and surgery; radiation and chemotherapy; surgery,
radiation and chemotherapy.
Comedo carcinoma in situ

A high grade type of in situ breast carcinoma with large poorly
differentiated cells and central necrosis. Also known as large cell in situ
carcinoma.
Complete local excision (CLE)

The complete excision of an entire tumour mass, surrounded on every
aspect by a margin of normal breast tissue, confirmed by histological
examination of the margins.
Coping strategies
Mental strategies or behaviours employed to maximise functioning and
reduce or eliminate psychological distress in response to stressful
situations. Coping strategies may be influenced by personality style and
the specific situation, and may change over time.
Core biopsy
The sampling of breast tissue with a cutting needle, 18 gauge or larger, to
give a tiny cylinder of tissue for histological examination. This technique
may involve a mechanical device to drive the cutting needle.
Cosmesis
The appearance of the breast following conservative treatment. It is
generally accepted that one goal of conservative treatment is to retain a
breast with an appearance as close to normal as is compatible with
effective treatment.
Counselling
Refers generically to a form of supportive care delivered by health
professionals. There are differing levels of sophistication depending on
the training and experiences of the practitioner involved.
Cribriform
See Non-comedo carcinoma in situ.
Cycle
Chemotherapy is usually administered at regular intervals depending on
the type of drugs. A cycle commences with the administration of the
chemotherapy and ends when the nadir has passed and the white blood
and platelet counts have returned to pretreatment values. Then the next
dose of chemotherapy is given.
Cytology
Assessment of cellular detail and abnormalities in a preparation of cells
obtained by fine needle aspiration (FNA), or by other methods such as
imprint or duct discharge cytology.
DCIS
Ductal carcinoma in situ.
Denial
Failure to acknowledge some aspect of external reality that would be
apparent to others. This is an involuntary reaction (as opposed to lying)
which aims to avoid anxiety.
Depression
A pervasive and sustained lowering of mood, often associated with
tearfulness, guilt or irritability. May also include loss of interest in
activities, lowered energy levels, impaired concentration and
disturbance of sleep and appetite.
Determination of disease extent

The use of clinical examination, imaging (X-rays, bone scans),
biochemical and pathologic information to determine the extent of the
underlying cancer.
Differentiation
The degree to which a tumour resembles normal tissue. In general, the
closer the resemblance, the better the prognosis. Well differentiated
tumours closely resemble normal tissue.
Disease-free survival
The time from the primary treatment of the breast cancer to the first
evidence of cancer recurrence.
DNA ploidy
A measure of the DNA content of a cell. Tumour growth is commonly
accompanied by accumulation of genetic abnormalities including
changes in the total amount of DNA per cell. From this comes the terms
diploid (normal complement of chromosomes), tetraploid, aneuploid or
polyploid.
Dry desquamation
A healing erythematous reaction with the shedding of dry skin.
Dysplasia
An abnormal growth of cells which have some of the features of
carcinoma cells but which have insufficient changes to warrant a
diagnosis of carcinoma. See also atypia. Note that this is a pathological
term and should be differentiated from the radiological term ‘dysplasia’,
which refers to an abnormal radiological appearance usually due to
fibrocystic disease.
ECOG
Eastern Cooperative Oncology Group. A United States group of
university and community oncologists funded to conduct trials to
combat cancer.
ECOG performance status

An arbitrary scale of symptoms and ambulation based on a five-point
scale developed by the United States Eastern Cooperative Oncology
Group:
0–No symptoms of cancer
1–Presence of cancer-related symptoms
2–Spends less than 50 per cent of daylight hours in bed
3–Spends more than 50 per cent, but less than 100 per cent of daylight
hours in bed
4–Totally confined to bed
EGF-R
Epidermal growth factor receptor. A cell surface growth factor receptor
which binds several peptide ligands, including EGF. A high expression of
EGF-R is associated with a poor prognosis. See also erbB-2.
Electron
The smallest particle of negative electricity. Electrons have a useful
property of finite penetration of tissue, as opposed to the exponential
absorption which occurs with X-rays.
EORTC
European Organization for Research and Treatment of Cancer. An
oncology cooperative which carries out multicentre clinical trials across
Europe.
EORTC core quality of life questionnaire (QLQ)

Developed by the EORTC study group for quality of life, QLQ - C30 is a
generic ‘core questionnaire’ relevant to any cancer to be used with
modules specific to a particular cancer. It has undergone extensive
translation and testing for interpretation and is available in most
European languages. A breast cancer module was field tested in 1995 in
Germany, Belgium, Denmark, Sweden, Spain, Portugal, France, Italy,
Poland, Bulgaria, Greece, Holland, Turkey and in all English-speaking
countries.
Epidermal growth factor receptor

See EGF-R.
ER
Oestrogen receptor. An intracellular receptor protein that binds
oestrogens and antioestrogens and mediates their effects by
subsequently binding to DNA and altering the expression of specific
genes. It is an indicator of responsiveness to hormonal therapies. High
ER expression is associated with a good prognosis and with a response
to hormonal therapy.
erbB-2
Also known as HER2/neu.A cell surface receptor related to EGF-R.
Activation of EGF-R and erbB-2 signal transduction pathways results in a
mitogenic response. High expression of erbB-2 is associated with a poor
prognosis.
Erythema
Redness of the skin which is the earliest sign of radiation reaction. It
usually occurs after a conventionally fractionated dose of about 40 Gray
has been delivered.
Extensive intraductal carcinoma (EIC)

EIC is generally said to exist when 25 per cent or more of the primary
invasive tumour mass is comprised of ductal carcinoma in situ (DCIS),
and when areas of DCIS co-exist in the adjacent breast tissue. EIC is a
predictor for high relapse rates following wide local excision and
radiotherapy.
Familial breast cancer

Breast cancer that generally occurs in the setting of a first degree
relative who has had breast cancer, particularly in pre-menopausal
disease, implying an inherited disposition. The two best described
syndromes of familial breast cancer are due to mutations of the BRCA1
gene (where there may also be a predisposition to ovarian cancer) and
mutations of the p53 gene (Li-Fraumeni syndrome). Familial breast
cancers are thought to comprise less than 10 per cent of all breast
cancers. Recently a second gene BRCA2, on chromosome 13, has also
been identified.
Fear
Anxiety due to a consciously recognised external threat or danger.
Fine needle aspiration biopsy (FNA or FNAB)

See fine needle biopsy.
Fine needle biopsy (FNB)

The sampling of cells from breast tissue for cytological examination
using a needle of size 23 gauge or smaller. When suction is applied
during the sampling, this is referred to as fine needle aspiration biopsy
(FNA or FNAB).
Fraction
The total dose of radiation to be given is usually delivered over several
weeks. That dose which is delivered each day is known as a fraction.
Free flap reconstruction

Soft tissue reconstruction where the tissue (such as the latissimus dorsi
or a TRAM flap) is separated from its donor site and a new blood supply
established using microsurgical techniques.
Frozen section
A rapid method of obtaining a histological diagnosis of tissue during an
operation. This is not routinely done for breast cancer.
G-CSF
Granulocyte cell stimulating factor. A natural substance which promotes
the release of mature white cells following their suppression, usually by
chemotherapy.
Genes
The functional units of heredity, each occupying a fixed location on a
chromosome within the cell nucleus.
Gene amplification
A process of DNA duplication that results in a chromosome having more
than one copy of a gene or genes and which can result in inappropriate
gene activation. It is a common mechanism of activation of oncogenes
such as erbB-2 and c-myc in breast cancer.
Grade
A relationship has been demonstrated between prognosis and degree of
differentiation of breast carcinoma. This degree of differentiation is
called the grade. A grade 1 carcinoma is well differentiated and is
associated with a good prognosis. A grade 2 carcinoma is moderately
differentiated and is associated with an intermediate prognosis. A grade
3 carcinoma is poorly differentiated and is associated with a poor
prognosis. Grade is assessed by a pathologist.
Gray
The modern unit of radiation dosage. Doses used in curative breast
cancer management would usually vary between 45 and 65 Gray. See
also rad.
Grief
The normal emotional response to loss, which may include a complex
range of painful feelings such as sadness, anger, helplessness, guilt and
despair.
Halsted mastectomy
See radical mastectomy.
HER2/neu
See erbB-2.
Histology
Assessment of cellular features by light microscopy of sections from
paraffin-embedded tissue.
Hormone receptors
Hormone receptors are proteins residing within the cell which
specifically bind to the appropriate hormone. This hormone receptor
complex subsequently stimulates the cell to undergo a physiological
function such as cell division. In women with breast cancer, these
receptors are present in approximately 50 per cent of all women and
are powerful prognostic indicators of survival and response to hormone
(or antihormonal) therapy.
Hormone replacement therapy (HRT)

The use of exogenous female hormones as a substitute for natural
hormones in women.
Hormone therapy
The use of drugs or hormones which specifically inhibit the growth of
hormone-responsive cancer cells.
Hyperplasia
Increased numbers of epithelial cells. If florid, there is a slightly
increased risk of developing subsequent breast carcinoma.
Immediate reconstruction
The reconstruction of the breast at the time of mastectomy.
In situ carcinoma
See carcinoma in situ.
Increment
See fraction.
International Breast Cancer Study Group

An international cooperative group which includes many Australian
clinical researchers. The group conducts multicentre trials, especially in
the area of adjuvant therapy.
Iridium (wire)
A radioactive wire sometimes used to deliver the boost to the operative
site in breast conserving techniques.
Karnofsky index
An index based on simple percentages ranging from 10–100, 100 being
totally normal and capable of full activity, and 10 being totally confined
to bed and close to death. See ECOG.
Ki67
Immunohistochemical marker of proliferative activity.
Labelling index
Also known as thymidine labelling index. A measure of proliferative
activity. The proportion of cells which incorporates radioactively
labelled thymidine over a given time. It is a method of estimating DNA
synthesis.
Large cell in situ carcinoma

See comedo carcinoma in situ.
Latissimus dorsi flap

Method of soft tissue reconstruction employing the skin of the back
carried on the latissimus dorsi muscle. A prosthesis may also be inserted
to provide greater volume.
LCIS
Lobular carcinoma in situ. It is a misnomer which describes a benign
proliferative process in the lobular units. It does not have specific
mammographic features and is usually detected by chance in the course
of a breast biopsy for another lesion.
Limited axillary dissection

Less than complete axillary clearance equivalent to low axillary
dissection.
Linear accelerator
Modern radiation equipment capable of delivering X-rays at very high
energies of up to 25 million electron volts (25MeV).
Loss of heterozygosity
The absence of one copy (allele) of a gene or of part of one copy of a
chromosome. In some circumstances, this may imply the presence of a
tumour suppressor gene in the lost genetic material.
Lumpectomy
Surgical removal of a lump from the breast. See complete local
excision.
Lymph nodes/lymph glands

Collections of lymphoid tissue at intervals throughout the body. A
common site or the early spread of breast cancer is to the axillary
lymph nodes.
Malignant
A tumour having the capacity to destroy locally, spread and cause death.
Mammogram
A soft tissue X-ray of the breast which may be undertaken to evaluate a
clinical problem or which may be undertaken as a screening test in
women with no symptoms of breast cancer.
Mammography
That process whereby soft tissue X-rays of the breast are obtained.
Margins of resection
The surgical margins of the excised tumour. See complete local
excision.
Mastectomy
Surgical removal of the breast. May be total (all of the breast) or partial.
See also radical (Halsted) mastectomy.
Megavoltage
Megavoltage applies to machines delivering X-rays of high energy. This
includes Cobalt 60 apparatus and modern linear accelerators.
Meta-analysis
A quantitative synthesis of the results of two or more primary studies
which have addressed the same hypothesis in the same way.
Metastasis
The process by which carcinoma cells are disseminated from the
tumour origin (primary tumour) to form a new tumour (secondary
tumour) at a distant site. Transportation of the cells is generally via
lymphatics or blood vessels.
Metastasise
See metastasis.
Metastatic cancer
Cancer which has spread to a site distant from the original primary site.
Micrometastases
Metastatic cancer which cannot be detected by conventional imaging
(X-ray, bone scans) or biochemical or haematological tests.
Micropapillary
See non-comedo carcinoma.
Mitosis
The process of cell division. The number of mitoses indicates the
number of tumour cells in replicative mode.
Modified radical mastectomy

Total mastectomy in continuity with a Level 2 or 3 axillary dissection,
without excision of the pectoralis major muscle and with or without
excision of the pectoralis minor muscles. See also Patey’s operation.
Moist desquamation
A response to radiation therapy characterised by denudation of the
epithelium. It can be exacerbated by friction and sweat and should
never be referred to as ‘radiation burn’.
Nadir
The lowest measured value. Usually used in the context of evaluating
the effect of chemotherapy or radiotherapy on the white blood cell and
platelet count.
Necrosis
The death of an individual cell or groups of cells in living tissue.
Sometimes seen in carcinomas.
Neutropenia (febrile)
That condition which exists when the numbers of circulating neutrophil
leucocytes are reduced. If the numbers fall to very low levels, there is
the risk of supervening infection and the syndrome is then known as
febrile neutropenia or neutropenic sepsis.
Nodal status
Indicates the histological presence or not of metastases in the axillary
nodes. (Node +ve = one or more nodes involved. Node -ve = no nodes
involved.)
Non-comedo carcinoma in situ

A low-grade type of in situ carcinoma comprising small cells. Includes
cribriform, micropapillary or small cell carcinoma depending on
pattern.
Occult metastases
Metastases not yet apparent.
Oestrogen receptor
See ER.
Oncogene
Literally, a cancer-causing gene. A gene, often with a normal function in
controlling growth or differentiation, which when functioning
abnormally (activated, for example, by amplification or mutation)
confers on normal cells immortality or the ability to form tumours
(transformation). Oncogenes that are commonly overexpressed or
amplified in breast cancer include EGF-R, erbB-2, c-myc, c-myb and
int-2/cyclin D1.
Open biopsy
A surgical procedure performed under local or general anaesthetic in
which a sample of breast tissue for histological examination is obtained
in a conventional surgical procedure, using an open incision.
Orthovoltage
X-rays delivered from generators operating at less than 500,000 volts
and usually in the region of 250,000–300,000 volts.
Ovarian ablation
Treatment which destroys ovarian function.
Overall survival
The time from the primary treatment of the breast cancer to the death
of the patient.
p53
A protein with complex functions that include mediating cell cycle
arrest after DNA damage. Li-Fraumeni syndrome (which results in a
marked increase in the risk of breast cancer) is associated with
inherited mutations of the p53 gene. Most p53 mutations result in an
abnormal protein which accumulates in cells and is thus easily
identified immunohistochemically. Acquired (somatic) mutations are
found in approximately 50 per cent of breast cancers.
Paget’s Disease of the Nipple

This is an eczematoid change of the nipple associated with an
underlying breast malignancy. About 1–2 per cent of patients with breast
cancer have it (from JM Dixon. ABC of breast disease BMJ Publishing
Group, 1995: p.35).
Palliation
The alleviation of symptoms due to the underlying cancer, without
prospect of cure.
Parallel pair
An arrangement of X-ray fields which allows radiation to be given in one
direction and in the reverse direction, and thus balance absorption with
depth.
Partial mastectomy
Excision of part of the breast. In practice synonymous with complete
local excision. See also mastectomy.
Patey’s operation
A modified radical operation for carcinoma of the breast in which the
breast and axillary lymph nodes are removed in continuity, as in the
Halsted operation, but without removal of the pectoralis major muscle.
See also modified radical mastectomy.
PCNA
Proliferating cell nuclear antigen. Protein expressed during S-phase and
therefore potentially a marker of proliferative fraction.
PR
Progesterone receptor. The intracellular receptor which binds progestins
and antiprogestins. It is an oestrogen-induced protein, so it can be used
as a marker of functional ER status. High expression of PR is associated
with a good prognosis.
Predictive factor
Frequently confused as a prognostic factor. An example is the oestrogen
receptor which is usually found in patients with good prognosis but
which is a predictive factor for response to hormone therapy.
Primary breast tumour

Tumour arising in the breast.
Progesterone receptor
See PR.
Prognostic factors
Patient or tumour parameters that are associated with, but not
necessarily causally related to, better or worse disease outcomes.
Progression
The continuing growth of the cancer. Often used when discussing
treatment failure. Also known as disease progression.
Prosthetic breast reconstruction

Creation of a breast shape using an artificial prosthesis, usually
consisting of a silicone envelope containing normal saline or silicone
gel.
Protocol
A well defined program for treatment.
pS2
An oestrogen-induced protein and therefore used as a marker of
functioning ER status. High expression of pS2 is associated with a good
prognosis.
Quadrantectomy
Strictly, excision of an entire quadrant of the breast. The term is often
incorrectly interchanged with segmentectomy or complete local
excision.
Quality of life
An individual’s overall appraisal of their situation and subjective sense
of wellbeing. Quality of life encompasses symptoms of disease and side
effects of treatment, functional capacity, social interactions and
relationships, and occupational functioning. Key psychological aspects
include subjective distress, satisfaction with treatment, existential issues,
and the impact of illness and treatment on sexuality and body image.
There are a number of standardised measures of quality of life, ranging
in sophistication from the simple visual scale through to comprehensive
self-administered questionnaires. Some questionnaires have been
designed for specific diseases or conditions, including several directed
specifically at cancer. These standardised measures have demonstrated
validity and reliability.
QLQ
See EORTC Core Quality of Life Questionnaire (QLQ).
Rad
An old unit of radiation dose, now superseded by the Gray. 1 Gray = 100
rads.
Radical (Halsted) mastectomy

Total mastectomy in continuity with a Level 3 axillary dissection and
complete excision of the pectoralis major and minor muscles. This
operation is now largely obsolete and rarely performed.
Radiotherapy
The use of radiation, usually X-rays or gamma rays, to kill tumour cells.
Rectus flap reconstruction

Soft tissue reconstruction using skin and fat from the abdomen carried
on the rectus abdominis muscle. Also known as TRAM — transverse
rectus abdominis myocutaneous flap.
Recurrence
Reappearance of the cancer after a period of remission.
Relapse
Reappearance of disease after observed response to treatment.
Response to therapy — complete response

The disappearance of all detectable cancer for a minimum of one
month. Also known as remission.
Response to therapy — disease progression
Increase of at least 25 per cent in the sum of the products (of the largest
diameter and its perpendicular) of all measurable disease for at least one
month, and no appearance of new lesions.
Response to therapy — partial response (partial remission)

A 50 per cent or greater reduction of the sum of the products (of the
largest diameter and its perpendicular) of all measurable disease for at
least one month, and no appearance of new lesions.
Response to therapy — stable disease

Measurable cancers (as defined above) without either response to
treatment or progression.
S-Phase fraction
A measure of proliferative activity. The proportion of cells synthesising
DNA (ie in the S-phase of the cell cycle), as estimated by flow
cytometry.
Scleroderma
A connective tissue disorder, primarily affecting the skin, oesophagus
and heart.
Secondary reconstruction
Reconstruction of the breast carried out some time after the original
mastectomy.
Secondary tumour
A deposit of breast cancer away from the breast (such as in the lung,
bone or lymph node). See metastasis.
Segmentectomy
The excision of an entire (radial) segment of the breast.
Sentinel node biopsy

Sampling of the first set of lymph nodes that receives drainage from the
tumour cells. A combination of radioactive tracer and colour dye is used
to localise the nodes. The biopsy technique is less extensive and can
reduce the need for axillary clearance in node negative patients. It is
not, at present, a standard procedure.
Simulator
Apparatus resembling a linear accelerator which allows rehearsal of the
treatment position and allows the calculation of the radiation treatment
prior to its commencement on a linear accelerator.
Small cell carcinoma

See non-comedo carcinoma in situ.
Soft tissue reconstruction

Method of reconstruction using the patient’s own tissue, transferred
from another area of the body.
Specimen X-ray
X-ray of a surgically removed specimen to confirm that a
mammographically detected lesion has been removed. Also used for
selection of histological sampling in impalpable lesions and a guide to
whether margins are adequate.
Staging
Conventionally refers to the allocation of categories (0, I, II, III, IV) to
groupings of tumours defined by internationally agreed criteria.
Frequently these are based on the tumour, the nodes and the metastases
(TNM). Staging may be based on clinical or pathological features.
Stereotaxis
A radiological technique to accurately localise a lesion in the breast.
Used to permit precise insertion of a needle in order to obtain material
for cytology (fine needle) or histology (core biopsy), or as an aid to
surgical excision of an impalpable lesion.
Subcutaneous mastectomy
Surgical excision of the entire breast parenchyma, including the axillary
tail of the breast, with preservation of the entire breast skin, including
the nipple and areola.
Support group
The existence or availability of people on whom an individual can rely
for the provision of emotional caring and concern, and reinforcement of
a sense of personal worth and value. Other components of support may
include provision of practical or material aid, information, guidance,
feedback and validation of the individual’s stressful experiences and
coping choices.
Systemic
Involving the whole body.
Tangents
Fields (radiotherapy target areas) which are planned in such a way that
the irradiation of a sector of the chest wall following mastectomy or
chest wall and breast following breast conserving surgery minimises
irradiation of the underlying lung.
Telangiectasia
Small dilated vessels which appear in heavily irradiated mucosal or
epithelial surfaces.
Teletherapy
Radiation therapy delivered from a distance by either Cobalt 60
apparatus or a linear accelerator.
Thymidine labelling index

See labelling index.
Tissue expansion
Creation of a breast shape using an inflatable silicone envelope placed
beneath the skin and muscle, which is gradually expanded over several
weeks by repeated injections of saline.
Total mastectomy
Surgical excision of the entire breast parenchyma including the axillary
tail of the breast, together with an ellipse of overlying skin which
encloses the nipple and areola.
Toxicity
Side effects which are due to the treatment administered. The side
effects range from mild to severe and are usually controllable, and in
some women are preventable.
Transverse rectus abdominis myocutaneous flap (TRAM)

See rectus flap reconstruction.
Treatment failure
The inability of the cancer therapy (whether surgery, radiation or
chemotherapy) to halt the growth or spread of the cancer.
Tubular carcinoma
A very well differentiated carcinoma seen increasingly as a result of
mammographic screening. The tumour needs to be 90 per cent tubular
to merit the term.
Tumour
An abnormal growth of tissue. It may be localised (benign) or invade
adjacent tissues (malignant) or distant tissues (metastatic).
Tumour suppressor gene

A gene which, when down-regulated, inactivated or lost (see loss of
heterozygosity), contributes to cell proliferation or ceases its activity
in blocking cell proliferation. Examples are p53 in breast cancer, RB
protein in retinoblastoma and possibly BRCA1 in breast cancer.
See anti-oncogene.
Tumour type
The overall histological pattern of the tumour.
Vascular infiltration
Invasion by carcinoma cells of peritumoral lymphatics or veins
indicating a propensity for distant spread.
Wedge
A beam modifying device which is used to correct for varying thickness
in a field of radiation. It is used in radiotherapy for breast cancer
because the thickness of the breast will vary from its apex to its base.
X-rays
X-rays are electromagnetic radiations with wave lengths in the range of
0.1–100 angstroms. X-rays are absorbed exponentially by the irradiated
tissue. See also electron.
REFERENCES
1. TNM classification of malignant tumours. New York: John Wiley & Sons
Inc, 1997.
2. Quality of Care and Health Outcomes Committee, NHMRC. Guidelines for
the development and implementation of clinical practice guidelines.
Canberra: AGPS, 1995.
3. Coates AS. Breast Cancer Consensus. Med J Aust 1994;161:S10–S16.
4. Coates A. Management of early breast cancer: an Australian consensus
report. Clinical Oncological Society of Australia, the Australian–New Zealand
Breast Cancer Trials Group, the Medical Oncology Group of Australia and
the Breast Section, Royal Australasian College of Surgeons. Oncology
1995;52:82–5.
5. Coates AS. Breast cancer consensus conference. Cancer Forum 1994;18:71.
6. Anonymous. Management of a newly diagnosed breast cancer: a national
approach to breast cancer control. Cancer Forum 1994;18:72–6.
7. Women’s perspectives sub-group NHMRC Working Party. Report on the
treatment of diagnosed breast cancer: what do women say about
treatment for breast cancer? 1994.
8. Carrick SE, Bonevski B, Redman S, et al. Surgeons’ opinions about the
NHMRC clinical practice guidelines for the management of early breast
cancer. Med J Aust 1998;169:300–5.
9. Ward JE, Boyages J, Gupta L. Local impact of the NHMRC early breast cancer
guidelines: where to from here? [see comments]. Med J Aust 1997;167:362–5.
10. Pelly JE, Newby L, Tito F, Redman S, Adrian AM. Clinical practice guidelines
before the law: sword or shield? [see comments]. Med J Aust 1998;169:330–3.
11. NHMRC NBCC. The management of early breast cancer for GPs: action
based on evidence. Woolloomooloo, NSW: NHMRC NBCC, 1997.
12. Turner J, Wooding S, Neil C. Psychosocial impact of breast cancer: a
summary of the literature. Woolloomooloo, NSW: NHMRC National Breast
Cancer Centre, 1996.
13. Burke S, Kissane D. Psychosocial support for breast cancer patients
provided by members of the treatment team. Woolloomooloo, NSW:
NHMRC NBCC, 1998.
14. National Health and Medical Research Council. Early breast cancer: a
consumer guide. Eastwood: The Stone Press, 1995.
15. National Breast Cancer Centre. All about early breast cancer.
Woolloomooloo NSW: NHMRC National Breast Cancer Centre, 1996.
16. iSource National Breast Cancer Centre. National survey of women’s views
about their care. Woolloomooloo NSW: NBCC, in preparation.
17. AIHW & AACR. Cancer in Australia 1995: Incidence and mortality data
for 1995 and selected for 1996. Canberra: AIHW, 1998.
18. AIHW. Breast & cervical screening in Australia, 1996–97. Canberra: AIHW,
1998.
19. Australian Institute of Health & Welfare, NHMRC NBCC. Breast cancer in
Australian women 1982–1996. Canberra: AIHW, 1999.
20. Smith CL, Kricker A, Armstrong BK. Breast cancer mortality trends in
Australia: 1921 to 1994 [published erratum appears in Med J Aust 1998 Mar
2;168(5):225]. Med J Aust 1998;168:11–4.
21. Australian Institute of Health and Welfare, Australasian Association of Cancer
Registries, NHMRC National Breast Cancer Centre. Breast cancer survival
in Australian women 1982–94. Canberra: Australian Institute of Health and
Welfare, 1998.
22. Hopper JL. Some public health issues in the current state of genetic testing
for breast cancer in Australia [see comments]. Aust N Z J Public Health
1996;20:467–72.
23. Higginson J, Muir C, Munoz N. Human cancer: epidemiology and
environmental causes. Cambridge: Cambridge University Press, 1992.
24. Ursin G, Bernstein L, Pike MC. Breast cancer. Cancer Surv 1994;19–20:241–64.
25. Henderson I, Schottenfeld D, Fraumeni J. Cancer epidemiology and
prevention. Oxford: Oxford University Press, 1996.
26. Beral V, Hermon C, Kay C, Hannaford P, et al. Mortality associated with oral
contraceptive use: 25 year follow-up of cohort of 46,000 women from
Royal College of General Practitioners’ oral contraception study [see
comments]. BMJ 1999;318:96–100.
27. Beral V, Banks E, Reeves G, Wallis M. Hormone replacement therapy and high
incidence of breast cancer between mammographic screens [letter;
comment] [see comments]. Lancet 1997;349:1103–4.
28. NHMRC National Breast Cancer Centre. Summary of risk factors for breast
cancer. Woolloomooloo: NHMRC National Breast Cancer Centre, 1999.
29. Huang Z, Hankinson SE, Colditz GA, et al. Dual effects of weight and weight
gain on breast cancer risk [see comments]. JAMA 1997;278:1407–11.
30. Kelsey JL, Whittemore AS. Epidemiology and primary prevention of cancers
of the breast, endometrium, and ovary. A brief overview. Ann Epidemiol
1994;4:89–95.
31. Longnecker MP, Newcomb PA, Mittendorf R, et al. Risk of breast cancer in
relation to lifetime alcohol consumption. J Natl Cancer Inst 1995;87:923–9.
32. Viladiu P, Izquierdo A, de Sanjose S, Bosch FX. A breast cancer case-control
study in Girona, Spain. Endocrine, familial and lifestyle factors. Eur J Cancer
Prev 1996;5:329–35.
33. Bodian CA. Benign breast diseases, carcinoma in situ, and breast cancer risk.
Epidemiol Rev 1993;15:177–87.
34. Hurley SF, Huggins RM, Snyder RD, Bishop JF.The cost of breast cancer
recurrences. Br J Cancer 1992;65:449–55.
35. Betsill WL, Jr., Rosen PP, Lieberman PH, Robbins GF. Intraductal carcinoma.
Long-term follow-up after treatment by biopsy alone. JAMA 1978;239:1863–
7.
36. Page DL, Dupont WD, Rogers LW, Landenberger M. Intraductal carcinoma of
the breast: follow-up after biopsy only. Cancer 1982;49:751–8.
37. Eusebi V, Feudale E, Foschini MP, Micheli A, et al. Long-term follow-up of in
situ carcinoma of the breast. Semin Diagn Pathol 1994;11:223–35.
38. Fisher B, Dignam J, Wolmark N, Mamounas E, et al. Lumpectomy and
radiation therapy for the treatment of intraductal breast cancer: findings
from National Surgical Adjuvant Breast and Bowel Project B-17. J Clin Oncol
1998;16:441–52.
39. Lagios MD, Margolin FR, Westdahl PR, Rose MR. Mammographically detected
duct carcinoma in situ. Frequency of local recurrence following tylectomy
and prognostic effect of nuclear grade on local recurrence. Cancer
1989;63:618–24.
40. Alpers CE, Wellings SR.The prevalence of carcinoma in situ in normal and
cancer-associated breasts. Hum Pathol 1985;16:796–807.
41. Fisher B, Costantino J, Redmond C, Fisher E, et al. Lumpectomy compared
with lumpectomy and radiation therapy for the treatment of intraductal
breast cancer [see comments]. N Engl J Med 1993;328:1581–6.
42. Julien JP, Bijker N, Fentiman IS, Peterse JL, et al. Radiotherapy in breast-
conserving treatment for ductal carcinoma in situ: first results of the
EORTC randomised phase III trial 10853. EORTC Breast Cancer
Cooperative Group and EORTC Radiotherapy Group [see comments].
Lancet 2000;355:528–33.
43. Schnitt SJ, Abner A, Gelman R, Connolly JL, et al.The relationship between
microscopic margins of resection and the risk of local recurrence in
patients with breast cancer treated with breast-conserving surgery and
radiation therapy [see comments]. Cancer 1994;74:1746–51.
44. Fisher B, Dignam J, Wolmark N, Wickerham DL, et al.Tamoxifen in treatment
of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel
Project B-24 randomised controlled trial [see comments]. Lancet
1999;353:1993–2000.
45. Fisher B, Costantino J, Redmond C, Poisson R, et al.A randomized clinical
trial evaluating tamoxifen in the treatment of patients with node-negative
breast cancer who have estrogen-receptor-positive tumors. N Engl J Med
1989;320:479–84.
46. Powles TJ, Tillyer CR, Jones AL, Ashley SE, et al. Prevention of breast cancer
with tamoxifen – an update on the Royal Marsden Hospital pilot
programme. Eur J Cancer 1990;26:680–4.
47. Powles TJ, Ashley S. Endometrial cancer during tamoxifen treatment. Lancet
1994;23:1048.
48. Fisher B, Costantino JP, Wickerham DL, Redmond CK, et al.Tamoxifen for
prevention of breast cancer: report of the National Surgical Adjuvant Breast
and Bowel Project P-1 Study [see comments]. J Natl Cancer Inst
1998;90:1371–88.
49. Page DL, Kidd TE, Jr, Dupont WD, Simpson JF, Rogers LW. Lobular neoplasia
of the breast: higher risk for subsequent invasive cancer predicted by more
extensive disease. Hum Pathol 1991;22:1232–9.
50. Hurley S, Hart S, Susil B. Prevalence, screening and management of
atypical hyperplasia and lobular carcinoma in situ. Woolloomooloo,
NSW: NHMRC NBCC, 1997.
51. Rosen PP, Kosloff C, Lieberman PH, Adair F, Braun DW, Jr. Lobular carcinoma
in situ of the breast. Detailed analysis of 99 patients with average follow-up
of 24 years. Am J Surg Pathol 1978;2:225–51.
52. Haagensen CD, Lane N, Lattes R, Bodian C. Lobular neoplasia (so-called
lobular carcinoma in situ) of the breast. Cancer 1978;42:737–69.
53. Dupont WD, Page DL. Risk factors for breast cancer in women with
proliferative breast disease. N Engl J Med 1985;312:146–51.
54. Carter CL, Corle DK, Micozzi MS, Schatzkin A, Taylor PR. A prospective study
of the development of breast cancer in 16,692 women with benign breast
disease. Am J Epidemiol 1988;128:467–77.
55. Dupont WD, Page DL. Relative risk of breast cancer varies with time since
diagnosis of atypical hyperplasia. Hum Pathol 1989;20:723–5.
56. Ford D, Easton DF, Peto J. Estimates of the gene frequency of BRCA1 and its
contribution to breast and ovarian cancer incidence. Am J Hum Genet
1995;57:1457–62.
57. Australian Cancer Network. Familial aspects of cancer: A guide to clinical
practice. Canberra: Commonwealth of Australia, 1999.
58. iSource National Breast Cancer Centre. Advice about familial aspects of
breast cancer and ovarian cancer: a guide for health professionals.
Woolloomooloo, NSW: NBCC, 2000.
59. NHMRC NBCC. Breast cancer and family history: what you need to know.
Woolloomooloo, NSW: NHMRC NBCC, 1997.
60. Kirk J,Tucker K. Best practice guidelines for familial cancer clinics.
Woolloomooloo, NSW: NHMRC NBCC, 1997.
61. Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status,
and survival in 24, 740 breast cancer cases. Cancer 1989;63:181–7.
62. Du Toit RS, Locker AP, Ellis IO, Elston CW, Blamey RW. Evaluation of the
prognostic value of triple node biopsy in early breast cancer. Br J Surg
1990;77:163–7.
63. Glick JH, Gelber RD, Goldhirsch A, Senn HJ. Meeting highlights: adjuvant
therapy for primary breast cancer [see comments]. J Natl Cancer Inst
1992;84:1479–85.
64. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The
value of histological grade in breast cancer: experience from a large study
with long-term follow-up. Histopathology 1991;19:403–10.
65. Henson DE, Ries L. Relationship among outcome, stage of disease and
histological grade in 22,616 cases of breast cancer. Cancer 1991;68:2124–49.
66. McGuire WL, Tandon AK, Allred DC, Chamness GC, Clark GM. How to use
prognostic factors in axillary node-negative breast cancer patients [see
comments]. J Natl Cancer Inst 1990;82:1006–15.
67. Fisher B, Redmond C, Fisher ER, Caplan R. Relative worth of estrogen or
progesterone receptor and pathologic characteristics of differentiation as
indicators of prognosis in node negative breast cancer patients: findings
from National Surgical Adjuvant Breast and Bowel Project Protocol B-06. J
Clin Oncol 1988;6:1076–87.
68. Kamby C, Andersen J, Ejlertsen B, Birkler NE, et al. Histological grade and
steroid receptor content of primary breast cancer – impact on prognosis
and possible modes of action. Br J Cancer 1988;58:480–6.
69. Rowland J, Holland J. Breast cancer handbook of psycho-oncology. London:
Oxford University Press, 1989.
70. Turner J, McGrath P. Needs of children of mothers with advanced breast
cancer. Sydney: NHMRC National Breast Cancer Centre, 1997.
71. Maguire P. Breast conservation versus mastectomy: psychological
considerations. Semin Surg Oncol 1989;5:137–44.
72. Turner J. Psychological issues in breast cancer. Unpublished 1994.
73. Turner J, Wooding S, Neil C. Psychosocial impact of breast cancer: a
summary of the literature 1986–1996. Woolloomooloo, NSW: NHMRC
National Breast Cancer Centre, 1998.
74. Pozo C, Carver CS, Noriega V, Harris SD, et al. Effects of mastectomy versus
lumpectomy on emotional adjustment to breast cancer: a prospective study
of the first year postsurgery. J Clin Oncol 1992;10:1292–8.
75. Rees B. Clinical practice guidelines for breast cancer treatment: counselling
and support input. Unpublished 1994.
76. Bloom JR, Kessler L. Risk and timing of counselling and support
interventions for younger women with breast cancer. J Natl Cancer Inst
Monogr 1994;199–206.
77. Ganz PA, Hirji K, Sim MS, Schag CA, et al. Predicting psychosocial risk in
patients with breast cancer. Med Care 1993;31:419–31.
78. Schag CA, Ganz PA, Polinsky ML, Fred C, et al. Characteristics of women at
risk for psychosocial distress in the year after breast cancer. J Clin Oncol
1993;11:783–93.
79. Maguire P, Tait A, Brooke M, Thomas C, Sellwood R. Effect of counselling on
the psychiatric morbidity associated with mastectomy. Br Med J
1980;281:1454–6.
80. Fallowfield LJ, Hall A, Maguire GP, Baum M. Psychological outcomes of
different treatment policies in women with early breast cancer outside a
clinical trial [see comments]. BMJ 1990;301:575–80.
81. Kissane DW, Bloch S, Burns WI. Psychological morbidity in the families of
patients with cancer. Psycho-oncology 1994;3:47–56.
82. Harrison J, Haddad P, Maguire P. The impact of cancer on key relatives: a
comparison of relative and patient concerns [see comments]. Eur J Cancer
1995;31A:1736–40.
83. Baider L, Kaplan De-Nour A. Adjustment to cancer: who is the patient – the
husband or the wife? Isr J Med Sci 1988;24:631–6.
84. Northouse LL, Cracchiolo-Caraway A, Appel CP. Psychologic consequences
of breast cancer on partner and family. Semin Oncol Nurs 1991;7:216–23.
85. Spiegel D, Bloom J, Gotheil E. Family environment as a predictor of
adjustment to metastatic breast cancer. Journal of Psychosocial Oncology
1983;1:33–44.
86. Mor V, Malin M, Allen S. Age differences in the psychosocial problems
encountered by breast cancer patients. J Natl Cancer Inst Monogr
1994;191–7.
87. Roberts CS, Cox CE, Shannon VJ, Wells NL. A closer look at social support as
a moderator of stress in breast cancer. Health Soc Work 1994;19:157–64.
88. Neuling SJ, Winefield HR. Social support and recovery after surgery for
breast cancer: frequency and correlates of supportive behaviours by family,
friends and surgeon. Soc Sci Med 1988;27:385–92.
89. Ell KO, Mantell JE, Hamovitch MB, et al. Social support, sense of control, and
coping among patients with breast, lung, or colorectal cancer. Journal of
Psychological Oncology 1989;7:63–89.
90. Zemore R, Shepel LF. Effects of breast cancer and mastectomy on emotional
support and adjustment. Soc Sci Med 1989;28:19–27.
91. Pistrang N, Barker C. The partner relationship in psychological response to
breast cancer. Soc Sci Med 1995;40:789–97.
92. Carter RE, Carter CA. Individual and marital adjustment in spouse pairs
subsequent to mastectomy. Am J Family Therapy 1993;40:291–300.
93. Schover LR, Yetman RJ, Tuason LJ, Meisler E, et al. Partial mastectomy and
breast reconstruction. A comparison of their effects on psychosocial
adjustment, body image, and sexuality. Cancer 1995;75:54–64.
94. NHMRC National Breast Cancer Centre. Psychosocial clinical practice
guidelines: providing information, support and counselling for women
with breast cancer. Canberra: Commonwealth of Australia, 2000.
95. Victorian ministerial women’s health working party. Why women’s health?
Victorian women respond. Victoria:Victoria & Commonwealth of Australia, 1987.
96. Fallowfield LJ. Quality of life measurement in breast cancer. J R Soc Med
1993;86:10–2.
97. Rogers v Whitaker. CLR 1992;175:489–90.
98. Butow PN, Maclean M, Dunn SM, Tattersall MH, Boyer MJ. The dynamics of
change: cancer patients’ preferences for information, involvement and
support [see comments]. Ann Oncol 1997;8:857–63.
99. Meredith C, Symonds P, Webster L, Lamont D, et al. Information needs of
cancer patients in west Scotland: cross sectional survey of patients’ views
[see comments]. BMJ 1996;313:724–6.
100. Lerman C, Daly M, Walsh WP, Resch N, et al. Communication between
patients with breast cancer and health care providers. Determinants and
implications. Cancer 1993;72:2612–20.
101. Roberts CS, Cox CE, Reintgen DS, Baile WF, Gibertini M. Influence of
physician communication on newly diagnosed breast patients’ psychologic
adjustment and decision-making. Cancer 1994;74:336–41.
102. Professional Education and Training Committee of the NSW Cancer Council
& the Postgraduate Medical Council of NSW. How to break bad news.
Sydney: NSW Cancer Council, 1994.
103. Lobb EA, Butow PN, Kenny DT, Tattersall MH. Communicating prognosis in
early breast cancer: do women understand the language used? [see
comments]. Med J Aust 1999;171:290–4.
104. Alderson P, Madden M, Oakley A, et al. Women’s views of breast cancer
treatment and research: Report of pilot project 1993. London: Social
Science Research Unit, University of London, 1994.
105. Clarke V, Lavery J, Ruffin C. A journey through breast cancer: reflections of
thirty survivors. Melbourne: Deakin University, 1993.
106. Suominen T. Breast cancer patients’ opportunities to participate in their
care. Cancer Nurs 1992;15:68–72.
107. Pierce PF. Deciding on breast cancer treatment: a description of decision
behavior. Nurs Res 1993;42:22–8.
108. Hilton BA. Issues, problems, and challenges for families coping with breast
cancer. Semin Oncol Nurs 1993;9:88–100.
109. Griffith P. Colliding with the system. In Cancer outcomes symposium.
Canberra: National Health & Medical Research Council & Department of
Human Services & Health, 1994.
110. National Health and Medical Research Council. General guidelines for
medical practitioners on providing information to patients. Canberra:
Australian Government Publishing Service, 1993.
111. Sutherland HJ, Llewellyn-Thomas HA, Lockwood GA,Tritchler DL,Till JE.
Cancer patients: their desire for information and participation in treatment
decisions. J R Soc Med 1989;82:260–3.
112. Siminoff LA, Fetting JH. Factors affecting treatment decisions for a life-
threatening illness: the case of medical treatment of breast cancer. Soc Sci
Med 1991;32:813–8.
113. Dunn SM, Butow PN, Tattersall MH, Jones QJ, et al. General information
tapes inhibit recall of the cancer consultation. J Clin Oncol 1993;11:2279–
85.
114. Waitzkin H. Doctor-patient communication. Clinical implications of social
scientific research. JAMA 1984;252:2441–6.
115. Butow PN, Dunn SM,Tattersall MH, Jones QJ. Patient participation in the
cancer consultation: evaluation of a question prompt sheet. Ann Oncol
1994;5:199–204.
116. Watson M, Denton S, Baum M, et al. Counselling breast cancer patients: a
specialist nurse service. Counselling Psychology Quarterly 1998;1.
117. Hogbin B, Jenkins VA, Parkin AJ . Remembering bad news consultations: an
evaluation of tape recorded consultations. Psycho-oncology 1992;1:147–54.
118. Damian D, Tattersall MH. Letters to patients: improving communication in
cancer care. Lancet 1991;338:923–5.
119. Berglund G, Bolund C, Gustafsson UL, Sjoden PO. One-year follow-up of the
‘Starting Again’ group rehabilitation programme for cancer patients. Eur J
Cancer 1994;30A:1744–51.
120. Devine EC, Westlake SK. The effects of psychoeducational care provided to
adults with cancer: meta-analysis of 116 studies. Oncol Nurs Forum
1995;22:1369–81.
121. Johnston M, Voegele C. Benefits of psychological preparation for surgery: a
meta-analysis. Annals of behavioural Medicine 1993;15:245–56.
122. Hathaway D. Effect of preoperative instruction on postoperative outcomes:
a meta-analysis. Nurs Res 1986;35:269–75.
123. McArdle JM, George WD, McArdle CS, Smith DC, et al. Psychological
support for patients undergoing breast cancer surgery: a randomised study
[see comments]. BMJ 1996;312:813–6.
124. Schnurre M. Helping the patient sing his own song. WHO Reg Publ Eur Ser
1992;44:388–95.
125. Meggison B. The best kind of support. Iowa Med 1989;79:373–4.
126. Caldwell J. Out of the breast cancer closet. Nurs BC 1993;25:18–20.
127. Dean C. Psychiatric morbidity following mastectomy: preoperative
predictors and types of illness [published erratum appears in J Psychosom
Res 1988;32(1):125]. J Psychosom Res 1987;31:385–92.
128. Bukberg J, Penman D, Holland JC. Depression in hospitalised cancer
patients. Psychosom Med 1984;46:199–212.
129. Kissane DW, Clarke DM, Ikin J, Bloch S, et al. Psychological morbidity and
quality of life in Australian women with early-stage breast cancer: a cross-
sectional survey [see comments]. Med J Aust 1998;169:192–6.
130. Pendlebury SC, Snars J. Role of a psychiatry liaison clinic in the management
of breast cancer. Australas Radiol 1996;40:283–6.
131. Hill D, Jamrozik K, White V, Collins J, Boyages J. Surgical management of
breast cancer in Australia in 1995. Woolloomooloo, NSW: NHMRC
132. Hill DJ, White VM, Giles GG, Collins JP, Kitchen PR. Changes in the
investigation and management of primary operable breast cancer in Victoria
[see comments]. Med J Aust 1994;161:110–1, 114, 118.
133. Byrne MJ, Jamrozik K, Parsons RW, Fitzgerald CJ et al. Breast cancer in
Western Australia in 1989. II. Diagnosis and primary management. Aust N Z
J Surg 1993;63:624–9.
134. Sainsbury R, Haward B, Rider L, Johnston C, Round C. Influence of clinician
workload and patterns of treatment on survival from breast cancer [see
comments]. Lancet 1995;345:1265–70.
135. Tulloh BR, Goldsworthy ME. Breast cancer management: a rural perspective.
Med J Aust 1997;166:26–9.
136. Antman K, Amato D, Wood W, Carson J, et al. Selection bias in clinical trials.
J Clin Oncol 1985;3:1142–7.
137. Davis S, Wright PW, Schulman SF, Hill LD, et al. Participants in prospective,
randomized clinical trials for resected non-small cell lung cancer have
improved survival compared with nonparticipants in such trials. Cancer
1985;56:1710–8.
138. Weijer C, Freedman B, Fuks A, Robbins J, et al.What difference does it make
to be treated in a clinical trial? A pilot study. Clin Invest Med 1996;19:179–83.
139. Cockburn J, Redman S, Kricker A. Should women take part in clinical trials
in breast cancer? Issues and some solutions. J Clin Oncol 1998;16:354–62.
140. Tretli S, Kvalheim G, Thoresen S, Host H. Survival of breast cancer patients
diagnosed during pregnancy or lactation. Br J Cancer 1988;58:382–4.
141. Clark RM, Chua T. Breast cancer and pregnancy: the ultimate challenge. Clin
Oncol (R Coll Radiol ) 1989;1:11–8.
142. Guinee VF, Olsson H, Moller T, Hess KR, et al. Effect of pregnancy on
prognosis for young women with breast cancer [see comments]. Lancet
1994;343:1587–9.
143. Zemlickis D, Lishner M, Degendorfer P, Panzarella T, et al. Maternal and fetal
outcome after breast cancer in pregnancy. Am J Obstet Gynecol
1992;166:781–7.
144. Petrek JA, Dukoff R, Rogatko A. Prognosis of pregnancy-associated breast
cancer [see comments]. Cancer 1991;67:869–72.
145. Mohle-Boetani J, Grosser S, Malec M, Whittemore AS. Survival advantage
among patients with breast cancer diagnosed at 45 to 49 years of age
[letter]. N Engl J Med 1986;315:587.
146. Saunders CM, Baum M. Breast cancer and pregnancy: a review [see
comments]. J R Soc Med 1993;86:162–5.
147. Ezzat A, Raja MA, Berry J, Zwaan FE, et al. Impact of pregnancy on non-
metastatic breast cancer: a case control study. Clin Oncol (R Coll Radiol )
1996;8:367–70.
148. Lethaby AE, O’Neill MA, Mason BH, Holdaway IM, Harvey VJ. Overall survival
from breast cancer in women pregnant or lactating at or after diagnosis.
Auckland Breast Cancer Study Group. Int J Cancer 1996;67:751–5.
149. Kroman N, Jensen MB, Melbye M, Wohlfahrt J, Mouridsen HT. Should women
be advised against pregnancy after breast-cancer treatment? Lancet
1997;350:319–22.
150. von Schoultz E, Johansson H, Wilking N, Rutqvist LE. Influence of prior and
subsequent pregnancy on breast cancer prognosis. J Clin Oncol
1995;13:430–4.
151. Danforth DN Jr. How subsequent pregnancy affects outcome in women
with a prior breast cancer. Oncology (Huntingt) 1991;5:23–30.
152. Rissanen PM. Pregnancy following treatment of mammary carcinoma. Acta
Radiol Ther Phys Biol 1969;8:415–22.
153. Bunker ML PM. Breast cancer associated with pregnancy or lactation. Am J
Obstet Gynecol 1963;85:312.
154. Dow KH, Harris JR, Roy C. Pregnancy after breast-conserving surgery and
radiation therapy for breast cancer. J Natl Cancer Inst Monogr 1994;131–7.
155. Begbie SD, Kerestes ZL, Bell DR. Patterns of alternative medicine use by
cancer patients [see comments]. Med J Aust 1996;165:545–8.
156. Downer SM, Cody MM, McCluskey P, Wilson PD, et al. Pursuit and practice
of complementary therapies by cancer patients receiving conventional
treatment [see comments]. BMJ 1994;309:86–9.
157. Cassileth BR, Lusk EJ, Strouse TB, Bodenheimer BJ. Contemporary
unorthodox treatments in cancer medicine. A study of patients, treatments,
and practitioners. Ann Intern Med 1984;101:105–12.
158. Harris L. Health information and the use of questionable treatments: a
study of the American public, 1987. Washington DC: Department of Health
and Human Services 1987, 1987.
159. Lerner IJ, Kennedy BJ.The prevalence of questionable methods of cancer
treatment in the United States. CA Cancer J Clin 1992;42:181–91.
160. Miller MJ, Boyer MJ, Dunn SM. Why do Australian cancer patients use
unproven treatments? Proceedings of the American Society of Clinical
Oncology 1995;22:76.
161. Sawyer MG, Gannoni AF,Toogood IR, Antoniou G, Rice M. The use of
alternative therapies by children with cancer [see comments]. Med J Aust
1994;160:320–2.
162. NHMRC iSource National Breast Cancer Centre. Clinical practice
guidelines for the management of advanced breast cancer. 2001.
163. Girgis A, Foot G. Satisfaction with breast cancer care: A summary of the
literature 1984-1994. Sydney: NHMRC NBCC, 1995.
164. Anonymous. Update on breast cancer. Sydney: 1994.
165. Ashley S, Royle GT, Corder A, Herbert A, et al. Clinical, radiological and
cytological diagnosis of breast cancer in young women. Br J Surg
1989;76:835–7.
166. Davies GC, Millis RR, Hayward JL. Assessment of axillary lymph node status.
Ann Surg 1980;192:148–51.
167. Fisher B, Wolmark N, Bauer M, Redmond C, Gebhardt M.The accuracy of
clinical nodal staging and of limited axillary dissection as a determinant of
histologic nodal status in carcinoma of the breast. Surg Gynecol Obstet
1981;152:765–72.
168. Somers RG, Sandler GL, Kaplan MJ, Najjar D, et al. Palpable abnormalities of
the breast not requiring excisional biopsy. Surg Gynecol Obstet
1992;175:325–8.
169. Irwig L, Macaskill P. Evidence relevant to guidelines for the investigation
of breast symptoms. Woolloomooloo, NSW: NHMRC National Breast Cancer
Centre, 1997.
170. National Breast Cancer Centre. The investigation of a new breast
symptom: a guide for general practitioners. Woolloomooloo, NSW: NHMRC
171. Stomper PC, Connolly JL. Mammographic features predicting an extensive
intraductal component in early-stage infiltrating ductal carcinoma. AJR Am J
Roentgenol 1992;158:269–72.
172. Holland R, Hendriks JH, Vebeek AL, Mravunac M, et al. Extent, distribution,
and mammographic/histological correlations of breast ductal carcinoma in
situ. Lancet 1990;335:519–22.
173. Madjar H, Ladner H, Sauerbrei W. Pre-operative staging of breast cancer by
palpation, mammography and high resolution ultrasound. Ultrasound in
obstetrics and gynaecology 1993;3:185–90.
174. Hirst C. Sonographic appearance of breast cancers 10mm or less in
diameter. Breast Ultrasound Update 1994;127–39.
175. Furnival CM, Hocking MA, Hughes HE, Reid MM, Blumgart LH. Aspiration
cytology in breast cancer. Its relevance to diagnosis. Lancet 1975;2:446–9.
176. Fajardo L. Stereotactic fine needle aspiration breast biopsy. In Parker S, Jobe
W. Percutaneous breast biopsy, New York: Raven Press, 1993.
177. Nicastri GR, Reed WP, Dziura BR.The accuracy of malignant diagnoses
established by fine-needle aspiration cytologic procedures of mammary
masses. Surg Gynaecol Obstet 1991;7:72–4.
178. Sterrett G, Harvey J, Parsons RW, Byrne MJ, et al. Breast cancer in Western
Australia in 1989 III. Accuracy of FNA cytology in diagnosis. Aust N Z J Surg
1994;64:745–9.
179. Parker SH, Lovin JD, Jobe WE, Burke BJ, et al. Nonpalpable breast lesions:
stereotactic automated large-core biopsies. Radiology 1991;180:403–7.
180. Boyages J, Recht A, Connolly J, Schnitt S, et al. Factors associated with local
recurrence as a first site of failure following the conservative treatment of
early breast cancer. Recent Results Cancer Res 1989;115:92–102.
181. Holland R, Veling SH, Mravunac M, Hendriks JH. Histologic multifocality of
Tis, T1–2 breast carcinomas. Implications for clinical trials of breast-
conserving surgery. Cancer 1985;56:979–90.
182. Australian Cancer Network Pathology Working Party. The pathology
reporting of breast cancer: a guide for pathologists, surgeons and
radiologists. Sydney: Australian Cancer Network, 1997.
183. 1997 update of recommendations for the use of tumor markers in breast
and colorectal cancer. Adopted on November 7, 1997 by the American
Society of Clinical Oncology. J Clin Oncol 1998;16:793–5.
184. van Diest PJ, Baak JP. The morphometric prognostic index is the strongest
prognosticator in premenopausal lymph node-negative and lymph node-
positive breast cancer patients. Hum Pathol 1991;22:326–30.
185. Henderson IC, Canellos GP. Cancer of the breast: the past decade (first of
two parts). N Engl J Med 1980;302:17–30.
186. Adair F, Berg J, Joubert L, Robbins GF. Long-term follow-up of breast cancer
patients: the 30-year report. Cancer 1974;33:1145–50.
187. Bates T, Riley DL, Houghton J, Fallowfield L, Baum M. Breast cancer in elderly
women: a Cancer Research Campaign trial comparing treatment with
tamoxifen and optimal surgery with tamoxifen alone. The Elderly Breast
Cancer Working Party. Br J Surg 1991;78:591–4.
188. Robertson JF, Ellis IO, Elston CW, Blamey RW. Mastectomy or tamoxifen as
initial therapy for operable breast cancer in elderly patients: 5-year follow-
up. Eur J Cancer 1992;28A:908–10.
189. National Institutes of Health. Consensus development statement: breast
cancer screening for women ages 40-49. 1997.
190. Calais G, Berger C, Descamps P, Chapet S, et al. Conservative treatment
feasibility with induction chemotherapy, surgery, and radiotherapy for
patients with breast carcinoma larger than 3 cm. Cancer 1994;74:1283–8.
191. Silverstein MJ, Gierson ED, Waisman JR, Senofsky GM, et al.Axillary lymph
node dissection for T1a breast carcinoma. Is it indicated? Cancer
1994;73:664–7.
192. Langlands AO, Prescott RJ, Hamilton T. A clinical trial in the management of
operable cancer of the breast. Br J Surg 1980;67:170–4.
193. Kaae S, Johansen H. Does simple mastectomy followed by irradiation offer
survival comparable to radical procedures? Int J Radiat Oncol Biol Phys
1977;2:1163–6.
194. Lythgoe JP, Palmer MK. Manchester regional breast study – 5 and 10 year
results. Br J Surg 1982;69:693–6.
195. Early Breast Cancer Triallists’ Collaborative Group. Effects of radiotherapy
and surgery in early breast cancer: an overview of the randomized trials.
New England Journal of Medicine 1995;335:1444–55.
196. Little JW SS.The finishing touches in nipple/areolar reconstruction.
Perspectives in plastic surgery 1988;2.
197. Carlson GW, Bostwick J, III, Styblo TM, Moore B, et al. Skin-sparing
mastectomy. Oncologic and reconstructive considerations. Ann Surg
1997;225:570–5.
198. Cheung KL, Blamey RW, Robertson JF, Elston CW, Ellis IO. Subcutaneous
mastectomy for primary breast cancer and ductal carcinoma in situ. Eur J
Surg Oncol 1997;23:343–7.
199. Kroll SS, Ames F, Singletary SE, Schusterman MA. The oncologic risks of skin
preservation at mastectomy when combined with immediate
reconstruction of the breast. Surg Gynecol Obstet 1991;172:17–20.
200. Collins J. The role of the surgeon. Cancer Forum 1994;18:92–5.
201. Veronesi U, Banfi A, Salvadori B, Luini A, et al. Breast conservation is the
treatment of choice in small breast cancer: long-term results of a
randomized trial [see comments]. Eur J Cancer 1990;26:668–70.
202. Fisher B, Redmond C, Poisson R, Margolese R, et al. Eight-year results of a
randomized clinical trial comparing total mastectomy and lumpectomy
with or without irradiation in the treatment of breast cancer [published
erratum appears in N Engl J Med May, 1994 19;330(20):1467] [see
comments]. N Engl J Med 1989;320:822–8.
203. Blichert-Toft M, Rose C, Andersen JA, Overgaard M, et al. Danish randomized
trial comparing breast conservation therapy with mastectomy: six years of
life-table analysis. Danish Breast Cancer Cooperative Group. J Natl Cancer
Inst Monogr 1992;19–25.
204. Fisher B, Anderson S, Fisher ER, Redmond C, et al. Significance of ipsilateral
breast tumour recurrence after lumpectomy [see comments]. Lancet
1991;338:327–31.
205. Fisher B, Redmond C, Fisher ER, Bauer M, et al.Ten-year results of a
randomized clinical trial comparing radical mastectomy and total
mastectomy with or without radiation. N Engl J Med 1985;312:674–81.
206. McCormick B, Yahalom J, Cox L, Shank B, Massie MJ.The patient’s
perception of her breast following radiation and limited surgery. Int J
Radiat Oncol Biol Phys 1989;17:1299–302.
207. Moyer A. Psychosocial outcomes of breast-conserving surgery versus
mastectomy: a meta-analytic review [published erratum appears in Health
Psychol 1997 Sep;16(5):442]. Health Psychol 1997;16:284–98.
208. Fallowfield LJ, Hall A, Maguire P, Baum M, A’Hern RP. Psychological effects of
being offered choice of surgery for breast cancer [see comments]. BMJ
1994;309:448.
209. Maguire GP, Lee EG, Bevington DJ, Kuchemann CS, et al. Psychiatric
problems in the first year after mastectomy. Br Med J 1978;1:963–5.
210. de Haes JC, Welvaart K. Quality of life after breast cancer surgery. J Surg
Oncol 1985;28:123–5.
211. Fallowfield LJ, Baum M, Maguire GP. Effects of breast conservation on
psychological morbidity associated with diagnosis and treatment of early
breast cancer. Br Med J (Clin Res Ed) 1986;293:1331–4.
212. Lasry JC, Margolese RG, Poisson R, Shibata H, et al. Depression and body
image following mastectomy and lumpectomy. J Chronic Dis 1987;40:529–34.
213. Kermeny MM, Wellisch DK, Schain WS. Psychosocial outcomes in a
randomised surgical trial for treatment of primary breast cancer. Cancer
1988;62:1231–7.
214. Lee MS, Love SB, Mitchell JB, Parker EM, et al. Mastectomy or conservation
for early breast cancer: psychological morbidity. Eur J Cancer
1992;28A:1340–4.
215. Schain WS, d’Angelo TM, Dunn ME, Lichter AS, Pierce LJ. Mastectomy versus
conservative surgery and radiation therapy. Psychosocial consequences.
Cancer 1994;73:1221–8.
216. Browning C,Thomas & Associates. Lymphoedema: prevalence, risk factors
and management: a review of research. Woolloomooloo, NSW: NHMRC
217. Cabanes PA, Salmon RJ, Vilcoq JR, Durand JC, et al.Value of axillary
dissection in addition to lumpectomy and radiotherapy in early breast
cancer. The Breast Carcinoma Collaborative Group of the Institut Curie [see
218. Hayward J, Caleffi M. The significance of local control in the primary
treatment of breast cancer. Lucy Wortham James clinical research award.
Arch Surg 1987;122:1244–7.
219. Fisher ER, Sass R, Fisher B. Pathologic findings from the National Surgical
Adjuvant Project for Breast Cancers (protocol no. 4). X. Discriminants for
tenth year treatment failure. Cancer 1984;53:712–23.
220. Overgaard M, Hansen PS, Overgaard J, Rose C, et al. Postoperative
radiotherapy in high-risk premenopausal women with breast cancer who
receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group
82b Trial [see comments]. N Engl J Med 1997;337:949–55.
221. Ragaz J, Jackson SM, Le N, Plenderleith IH, et al.Adjuvant radiotherapy and
chemotherapy in node-positive premenopausal women with breast cancer
[see comments]. N Engl J Med 1997;337:956–62.
222. Steele RJ, Forrest AP, Gibson T, Stewart HJ, Chetty U. The efficacy of lower
axillary sampling in obtaining lymph node status in breast cancer: a
controlled randomized trial. Br J Surg 1985;72:368–9.
223. Chetty U, Jack W, Prescott RJ, Tyler C, Rodger A. Management of the axilla in
operable breast cancer treated by breast conservation: a randomized
clinical trial. Edinburgh Breast Unit. Br J Surg 2000;87:163–9.
224. Kissin MW, Thompson EM, Price AB, Slavin G, Kark AE. The inadequacy of
axillary sampling in breast cancer. Lancet 1982;1:1210–2.
225. Krag D, Weaver D, Ashikaga T, Moffat F, et al.The sentinel node in breast
cancer – a multicenter validation study [see comments]. N Engl J Med
1998;339:941–6.
226. Veronesi U, Paganelli G, Galimberti V, Viale G, et al. Sentinel-node biopsy to
avoid axillary dissection in breast cancer with clinically negative lymph-
nodes [see comments]. Lancet 1997;349:1864–7.
227. Overgaard M, Hansen PS, Overgaard C, et al. Randomized trial evaluating
postoperative radiotherapy in high-risk postmenopausal breast cancer
patients given adjuvent tamoxifen. Results from the DBCG 82C Trial.
Radiotherapy and oncology 1998;48:586.
228. Early Breast Cancer Triallists’ Collaborative Group. Favourable and
unfavourable effects on long-term survival of radiotherapy for early breast
cancer: an overview of the randomized trials. Lancet 2000;355:1757–70.
229. Baum M, Haybittle JH, Berstock DA, et al. Cancer research campaign (Kings/
Cambridge) Trial for early breast cancer – a detailed update at the tenth
year. Lancet 1980;2:55–60.
230. Pisansky TM, Ingle JN, Schaid DJ, Hass AC, et al. Patterns of tumor relapse
following mastectomy and adjuvant systemic therapy in patients with
axillary lymph node-positive breast cancer. Impact of clinical,
histopathologic, and flow cytometric factors [published erratum appears in
Cancer 1993 Oct 15;72(8):2524]. Cancer 1993;72:1247–60.
231. Fowble B, Gray R, Gilchrist K, Goodman RL, et al. Identification of a
subgroup of patients with breast cancer and histologically positive axillary
nodes receiving adjuvant chemotherapy who may benefit from
postoperative radiotherapy. J Clin Oncol 1988;6:1107–17.
232. Fisher BJ, Perera FE, Cooke AL, Opeitum A, et al. Long-term follow-up of
axillary node-positive breast cancer patients receiving adjuvant systemic
therapy alone: patterns of recurrence. Int J Radiat Oncol Biol Phys
1997;38:541–50.
233. Vincini F, Horwitz E, Lacerna M, et al.The role of regional nodal irradiation
in the management of patients with early-stage breast cancer treated with
breast-conserving therapy. Int J Radiat Oncol Biol Phys 1997;38:1069–76.
234. Ung O, Langlands AO, Barraclough B, Boyages J. Combined chemotherapy
and radiotherapy for patients with breast cancer and extensive nodal
involvement. J Clin Oncol 1995;13:435–43.
235. Diab SG, Hilsenbeck SG, de Moor C, Clark GM, et al. Radiation therapy and
survival in breast cancer patients with 10 or more positive axillary lymph
nodes treated with mastectomy. J Clin Oncol 1998;16:1655–60.
236. Gilboa D, Borenstein A, Floro S, Shafir R, et al. Emotional and psychosocial
adjustment of women to breast reconstruction and detection of subgroups
at risk for psychological morbidity. Ann Plast Surg 1990;25:397–401.
237. Burcham J. Breast reconstruction: a review of the research and patient
and professional resources. Woolloomooloo, NSW: NHMRC National Breast
238. Barraclough B. Breast reconstruction – immediate or delayed. World
Congress of Surgery, 1997.
239. Stevens LA, McGrath MH, Druss RG, Kister SJ, et al.The psychological
impact of immediate breast reconstruction for women with early breast
cancer. Plast Reconstr Surg 1984;73:619–28.
240. Bostwick J, III. Reconstruction after mastectomy. Surg Clin North Am
1990;70:1125–40.
241. Armstrong RW, Berkowitz RL, Bolding F. Infection following breast
reconstruction [see comments]. Ann Plast Surg 1989;23:284–8.
242. Marshall DR. The contralateral breast flap in reconstruction of the breast
and chest wall. Ann Plast Surg 1993;31:508–13.
243. Moore TS, Farrell LD. Latissimus dorsi myocutaneous flap for breast
reconstruction: long-term results. Plast Reconstr Surg 1992;89:666–72.
244. Feller AM. Free TRAM. Results and abdominal wall function. Clin Plast Surg
1994;21:223–32.
245. Beasley ME.The pedicled TRAM as preference for immediate autogenous
tissue breast reconstruction. Clin Plast Surg 1994;21:191–205.
246. Brooks PM. Silicone breast implantation: doubts about the fears. Med J Aust
1995;162:432–4.
247. Rowland JH, Holland JC, Chaglassian T, Kinne D. Psychological response to
breast reconstruction. Expectations for and impact on postmastectomy
functioning. Psychosomatics 1993;34:241–50.
248. Schain WS, Wellisch DK, Pasnau RO, Landsverk J.The sooner the better: a
study of psychological factors in women undergoing immediate versus
delayed breast reconstruction. Am J Psychiatry 1985;142:40–6.
249. Dean C, Chetty U, Forrest AP. Effects of immediate breast reconstruction on
psychosocial morbidity after mastectomy. Lancet 1983;1:459–62.
250. Tanner R, Abraham SF, Llewellyn-Jones D. External breast prostheses. A
survey of their use by women after mastectomy. Med J Aust 1983;1:270–2.
251. Brennan MJ, Miller LT. Overview of treatment options and review of the
current role and use of compression garments, intermittent pumps, and
exercise in the management of lymphedema. Cancer 1998;83:2821–7.
252. Tobin MB, Lacey HJ, Meyer L, Mortimer PS. The psychological morbidity of
breast cancer-related arm swelling. Psychological morbidity of
lymphoedema. Cancer 1993;72:3248–52.
253. Woods M,Tobin M, Mortimer P. The psychosocial morbidity of breast cancer
patients with lymphoedema. Cancer Nurs 1995;18:467–71.
254. Mirilo BR, Bunce I, Chapman M. Psychosocial benefits of post-mastectomy
lymphoedema therapy. Cancer Nurs 1995;18:197–205.
255. Velanovich V, Szymanski W. Quality of life of breast cancer patients with
lymphedema. Am J Surg 1999;177:184–7.
256. Horowitz SA, Passiki SD, Brish M, Breitbart WS. A group intervention for staff
on a neuro-oncology service. Psycho-oncology 1994;3:329–32.
257. Kattlove H, Liberati A, Keeler E, Brook RH. Benefits and costs of screening
and treatment for early breast cancer. Development of a basic benefit
package [see comments]. JAMA 1995;273:142–8.
258. Butler JR, Furnival CM, Hart RF. The costs of treating breast cancer in
Australia and the implications for breast cancer screening. Aust N Z J Surg
1995;65:485–91.
259. Butler JR, Howarth A. Out-of-pocket expenses incurred by women for
diagnosis and treatment of breast cancer in Australia. Woolloomooloo,
NSW: NHMRC National Breast Cancer Centre, 1999.
260. Liljegren G, Holmberg L, Adami HO, Westman G, et al. Sector resection with
or without postoperative radiotherapy for stage I breast cancer: five-year
results of a randomized trial. Uppsala-Orebro Breast Cancer Study Group
[see comments]. J Natl Cancer Inst 1994;86:717–22.
261. Liljegren G, Holmberg L, Bergh J, Lindgren A, et al. 10-Year results after
sector resection with or without postoperative radiotherapy for stage I
breast cancer: a randomized trial [see comments]. J Clin Oncol
1999;17:2326–33.
262. Fisher B, Anderson S, Redmond CK, Wolmark N, et al. Reanalysis and results
after 12 years of follow-up in a randomized clinical trial comparing total
mastectomy with lumpectomy with or without irradiation in the treatment
of breast cancer [see comments]. N Engl J Med 1995;333:1456–61.
263. Fisher ER, Leeming R, Anderson S, Redmond C, Fisher B. Conservative
management of intraductal carcinoma (DCIS) of the breast. Collaborating
NSABP investigators. J Surg Oncol 1991;47:139–47.
264. Schnitt SJ, Connolly JL, Khettry U, Mazoujian G, et al. Pathologic findings on
re-excision of the primary site in breast cancer patients considered for
treatment by primary radiation therapy. Cancer 1987;59:675–81.
265. Veronesi U, Luini A, Del Vecchio M, Greco M, et al. Radiotherapy after
breast-preserving surgery in women with localized cancer of the breast
[see comments]. N Engl J Med 1993;328:1587–91.
266. Peto R, Clarke M, Collins R, et al. Facts and figures from the meta-analyses in
breast cancer. Eur J Cancer 1998;34.
267. Baum M. The Skinner Lecture: a cost-benefit analysis of postoperative
radiotherapy in the treatment of early breast cancer. Clin Oncol (R Coll
Radiol) 1991;3:223–9.
268. Stewart HJ, Jack WL, Everington D, et al. South-East Scottish trial of local
therapy in node-negative breast cancer. Breast 1994;3:31–9.
269. Ghersi D, Simes J. Report of the effectiveness of post-mastectomy
radiotherapy and risk factors for local recurrence in early breast cancer. In
Radiation Oncology Advisory Group of the National Breast Cancer Centre
and the faculty of Radiation Oncology of the Royal Australian and New
Zealand College of Radiologists. Woolloomooloo, NSW: NHMRC National
Breast Cancer Centre, 1999.
270. Cuzick J, Stewart H, Peto R, Baum M, et al. Overview of randomized trials of
postoperative adjuvant radiotherapy in breast cancer. Cancer Treat Rep
1987;71:15–29.
271. Cuzick J, Stewart HJ, Peto R, Baum M, et al. Overview of randomized trials of
postoperative adjuvant radiotherapy in breast cancer. Recent Results
Cancer Res 1988;111:108–29.
272. Cuzick J, Stewart H, Rutqvist L, Houghton J, et al. Cause-specific mortality in
long-term survivors of breast cancer who participated in trials of
radiotherapy [see comments]. J Clin Oncol 1994;12:447–53.
273. Whelan TJ, Julian J, Wright J, Jadad AR, Levine ML. Does locoregional
radiation therapy improve survival in breast cancer? A meta-analysis. J Clin
Oncol 2000;18:1220–9.
274. Ragaz J. Can post-mastectomy locoregional radiotherapy affect systemic
recurrences in medium risk breast cancer subsets treated with adjuvant
chemotherapy? mini symposium 3. Postoperative radiotherapy for breast
cancer. San Antonio: 21st annual San Antonio Breast Cancer Symposium, 1998.
275. Fisher BJ, Perera FE, Cooke AL, Opeitum A, et al. Extracapsular axillary node
extension in patients receiving adjuvant systemic therapy: an indication for
radiotherapy? Int J Radiat Oncol Biol Phys 1997;38:551–9.
276. Donegan WL, Stine SB, Samter TG. Implications of extracapsular nodal
metastases for treatment and prognosis of breast cancer. Cancer
1993;72:778–82.
277. Leonard C, Corkill M, Tompkin J, Zhen B, et al.Are axillary recurrence and
overall survival affected by axillary extranodal tumor extension in breast
cancer? Implications for radiation therapy. J Clin Oncol 1995;13:47–53.
278. NHMRC National Breast Centre Centre. Radiotherapy and Breast Cancer.
Woolloomooloo, NSW: NHMRC National Breast Cancer Centre, 1999.
279. Irwig L, Bennetts A. Impact of radiotherapy on quality of life. 1994.
280. Taylor ME, Perez CA, Halverson KJ, Kuske RR, et al. Factors influencing
cosmetic results after conservation therapy for breast cancer. Int J Radiat
Oncol Biol Phys 1995;31:753–64.
281. Olivotto IA, Rose MA, Osteen RT, Love S, et al. Late cosmetic outcome after
conservative surgery and radiotherapy: analysis of causes of cosmetic
failure. Int J Radiat Oncol Biol Phys 1989;17:747–53.
282. Rodger A, Corbett PJ, Chetty U. Lactation after breast conserving therapy,
including radiation therapy, for early breast cancer. Radiother Oncol
1989;15:243–4.
283. Dodwell DJ, Langlands A. Cardiac morbidity of post-operative adjuvant
radiotherapy for breast cancer. A review. Australas Radiol 1994;38:154–6.
284. Rutqvist LE, Liedberg A, Hammar N, Dalberg K. Myocardial infarction among
women with early-stage breast cancer treated with conservative surgery
and breast irradiation. Int J Radiat Oncol Biol Phys 1998;40:359–63.
285. Gyenes G, Gagliardi G, Lax I, Fornander T, Rutqvist LE. Evaluation of
irradiated heart volumes in stage I breast cancer patients treated with
postoperative adjuvant radiotherapy. J Clin Oncol 1997;15:1348–53.
286. Hojris I, Overgaard M, Christensen JJ, Overgaard J. Morbidity and mortality
of ischaemic heart disease in high-risk breast-cancer patients after adjuvant
postmastectomy systemic treatment with or without radiotherapy: analysis
of DBCG 82b and 82c randomised trials. Radiotherapy Committee of the
Danish Breast Cancer Cooperative Group. Lancet 1999;354:1425–30.
287. The Steering Committee on clinical practice guidelines for the care and
treatment of breast cancer. Breast radiotherapy after breast-conserving
surgery. CMAJ 1998;158:35–42.
288. Pierquin B, Mazeron JJ, Glaubiger D. Conservative treatment of breast cancer
in Europe: report of the Groupe Européen de Curietherapie. Radiother
Oncol 1986;6:187–98.
289. Powell S, Cooke J, Parsons C. Radiation-induced brachial plexus injury:
follow-up of two different fractionation schedules. Radiother Oncol
1990;18:213–20.
290. Doherty MA, Rodger A, Langlands AO, Kerr GR. Multiple primary tumours in
patients treated with radiotherapy for breast cancer. Radiother Oncol
1993;26:125–31.
291. Pendlebury SC, Bilous M, Langlands AO. Sarcomas following radiation
therapy for breast cancer: a report of three cases and a review of the
literature. Int J Radiat Oncol Biol Phys 1995;31:405–10.
292. Shelley W, Brundage M, Hayter C, Paszat L, et al.A shorter fractionation
schedule for postlumpectomy breast cancer patients. Int J Radiat Oncol
Biol Phys 2000;47:1219–28.
293. Lamb D, Atkinson C, Joseph D, O’Brien P, et al. Simultaneous adjuvant
radiotherapy and chemotherapy for stage I and II breast cancer. Australas
Radiol 1999;43:220–6.
294. Early Breast Cancer Triallists’ Collaborative Group. Systemic treatment of
early breast cancer by hormonal, cytotoxic or immune therapy: 133
randomised trials involving 31,000 recurrences and 24,000 deaths among
75,000 women. Lancet 1992;339:1–15.
295. Early Breast Cancer Triallists’ Collaborative Group. Systemic treatment of
early breast cancer by hormonal, cytotoxic or immune therapy: 133
randomized trials involving 31,000 recurrences and 24,000 deaths among
75,000 women. Lancet 1992;339:71–85.
296. Anonymous. Adjuvant systemic therapy for early breast cancer. Lancet
1992;339:27.
297. Early Breast Cancer Triallists’ Collaborative Group. Tamoxifen for early
breast cancer: an overview of the randomised trials. [see comments]. Lancet
1998;351:1451–67.
298. Early Breast Cancer Triallists’ Collaborative Group. Polychemotherapy for
early breast cancer: an overview of the randomised trials. [see comments].
Lancet 1998;352:930–42.
299. Early Breast Cancer Triallists’ Collaborative Group. Ovarian ablation in early
breast cancer: overview of the randomised trials. Lancet 1996;348:1189–96.
300. Scottish Cancer Trials Breast Group and ICRF Breast Unit GH. Adjuvant
ovarian ablation versus CMF chemotherapy in premenopausal women with
pathological stage II breast carcinoma: the Scottish trial. Scottish Cancer
Trials Breast Group and ICRF Breast Unit, Guy’s Hospital, London [see
301. Fisher B, Brown A, Mamounas E, Wieand S, et al. Effect of preoperative
chemotherapy on local-regional disease in women with operable breast
cancer: findings from National Surgical Adjuvant Breast and Bowel Project
B-18 [see comments]. J Clin Oncol 1997;15:2483–93.
302. Harris L, Swain SM. The role of primary chemotherapy in early breast
cancer. Semin Oncol 1996;23:31–42.
303. Zambetti M, Valagussa P, Bonadonna G. Eight-year results with adjuvant IV
CMF in node-negative (n-) and estrogen receptor-negative (ER-) breast
cancer. Proc Ann Meeting Am Soc Clin Oncol 1992;11.
304. Engelsman E, Klijn JC, Rubens RD, Wildiers J, et al.‘Classical’ CMF versus a 3-
weekly intravenous CMF schedule in postmenopausal patients with
advanced breast cancer. An EORTC Breast Cancer Co-operative Group Phase
III Trial (10808). Eur J Cancer 1991;27:966–70.
305. Goldhirsch A, Colleoni M, Coates AS, Castiglione-Gertsch M, Gelber RD.
Adding adjuvant CMF chemotherapy to either radiotherapy or tamoxifen:
are all CMFs alike? The International Breast Cancer Study Group (IBCSG).
Ann Oncol 1998;9:489–93.
306. Goldhirsch A, Coates AS, Colleoni M, Castiglione-Gertsch M, Gelber RD.
Adjuvant chemoendocrine therapy in postmenopausal breast cancer:
cyclophosphamide, methotrexate, and fluorouracil dose and schedule may
make a difference. International Breast Cancer Study Group. J Clin Oncol
1998;16:1358–62.
307. Levine MN, Bramwell VH, Pritchard KI, Norris BD, et al. Randomized trial of
intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy
compared with cyclophosphamide, methotrexate, and fluorouracil in
premenopausal women with node-positive breast cancer. National Cancer
Institute of Canada Clinical Trials Group [see comments]. J Clin Oncol
1998;16:2651–8.
308. Hutchins LF, Green S, Ravdin P. CMF versus CAF with and without tamoxifen
in high risk node-negative breast cancer patients and a natural history
follow-up study in low risk node negative patients: first results of
intergroup trial 0102. Proc Ann Meeting Am Soc Clin Oncol 1998;17.
309. Henderson IC, Berry D, Demetri G. Improved disease free survival and
overall survival from the addition of sequential paclitaxel but not from the
escalation of doxorubicin dose level in the adjuvant chemotherapy of
patients with node-positive primary breast cancer. Proc Ann Meeting Am
Soc Clin Oncol 1998;17.
310. Bonadonna G, Valagussa P. Dose-response effect of adjuvant chemotherapy
in breast cancer. N Engl J Med 1981;304:10–5.
311. Wood WC, Budman DR, Korzun AH, Cooper MR, et al. Dose and dose
intensity of adjuvant chemotherapy for stage II, node-positive breast
carcinoma [see comments] [published erratum appears in N Engl J Med
1994 Jul 14,331(2):139]. N Engl J Med 1994;330:1253–9.
312. Meisenberg BR, Ross M, Vredenburgh JJ, Jones R, et al. Randomized trial of
high-dose chemotherapy with autologous bone marrow support as
adjuvant therapy for high-risk, multi-node-positive malignant melanoma [see
313. Peters WP, Ross M, Vredenburgh JJ, Meisenberg B, et al. High-dose
chemotherapy and autologous bone marrow support as consolidation after
standard-dose adjuvant therapy for high-risk primary breast cancer. J Clin
Oncol 1993;11:1132–43.
314. Hortobagyi G.N., Buzdar AU, Champlin R. Lack of efficacy of adjuvant high
dose tandem combination chemotherapy for high risk primary breast
cancer. Proc Ann Meeting Am Soc Clin Oncol 1998;17.
315. Rodenhuis S, Richel DJ, van der WE, Schornagel JH, et al. Randomised trial of
high-dose chemotherapy and haemopoietic progenitor-cell support in
operable breast cancer with extensive axillary lymph-node involvement
[see comments]. Lancet 1998;352:515–21.
316. Talbot S, Basser R, Boyle F, Gallelari M, et al. Review of high-dose
chemotherapy as a treatment strategy for breast cancer. iSource National
Breast Cancer Centre, (in preparation).
317. Anonymous. American Society of Clinical Oncology recommendations for
the use of hemopoietic colony-stimulating factors: evidence-based, clinical
practice guidelines. J Clin Oncol 1994;12:2471–508.
318. Coates A, Abraham S, Kaye SB, Sowerbutts T, et al. On the receiving
end – patient perception of the side-effects of cancer chemotherapy. Eur J
Cancer Clin Oncol 1983;19:203–8.
319. Marschner N. Anti-emetic control with ondansetron in the chemotherapy of
breast cancer: a review. Eur J Cancer 1991;27 Suppl 1:S15–S17.
320. Griffin AM, Butow PN, Coates AS, Childs AM, et al. On the receiving end. V:
Patient perceptions of the side effects of cancer chemotherapy in 1993.
Ann Oncol 1996;7:189–95.
321. Coates A, Gebski V, Bishop JF, Jeal PN, et al. Improving the quality of life
during chemotherapy for advanced breast cancer. A comparison of
intermittent and continuous treatment strategies. N Engl J Med
1987;317:1490–5.
322. Harris J, Morrow M, Bonadonna G. Cancer of the breast. In de Vita V, Hellman
S, Rosenberg S. Cancer: Principles and Practice of Oncology (4th ed),
Philadelphia: JB Lippincott, 1993: 1264–1332.
323. Ganz PA, Rowland JH, Desmond K, Meyerowitz BE, Wyatt GE. Life after
breast cancer: understanding women’s health-related quality of life and
sexual functioning. J Clin Oncol 1998;16:501–14.
324. Dorval M, Maunsell E, Deschenes L, Brisson J, Masse B. Long-term quality of
life after breast cancer: comparison of 8-year survivors with population
controls. J Clin Oncol 1998;16:487–94.
325. Curran D, van Dongen JP, Aaronson NK, Kiebert G, et al. Quality of life of
early-stage breast cancer patients treated with radical mastectomy or breast-
conserving procedures: results of EORTC Trial 10801. The European
Organization for Research and Treatment of Cancer (EORTC), Breast Cancer
Co-operative Group (BCCG). Eur J Cancer 1998;34:307–14.
326. Lindley C, Vasa S, Sawyer WT, Winer EP. Quality of life and preferences for
treatment following systemic adjuvant therapy for early-stage breast cancer.
J Clin Oncol 1998;16:1380–7.
327. Kaplan HS. A neglected issue: the sexual side effects of current treatments
for breast cancer. J Sex Marital Ther 1992;18:3–19.
328. Kissane D, White K, Cooper K, Vitetta L. Psychosocial support in the area of
sexuality and body image for women with breast cancer. (in preparation).
Woolloomooloo, NSW: iSource National Breast Cancer Centre.
329. Weineke MH, Dienst ET. Neuropsychological assessment of cognitive
functioning following chemotherapy for breast cancer. Psycho-oncology
1995;4:61–6.
330. van Dam FS, Schagen SB, Muller MJ, Boogerd W, et al. Impairment of
cognitive function in women receiving adjuvant treatment for high-risk
breast cancer: high-dose versus standard-dose chemotherapy [see
331. Schagan SB, van Dam FS, Muller MJ. Cognitive deficits after post operative
adjuvant chemotherapy for breast cancer. Cancer 1999;85:640–50.
332. Curtis RE, Boice JD, Jr Stovall M, Bernstein L, et al. Risk of leukemia after
chemotherapy and radiation treatment for breast cancer [see comments]. N
Engl J Med 1992;326:1745–51.
333. Young-McCaughan S. Sexual functioning in women with breast cancer after
treatment with adjuvant therapy. Cancer Nurs 1996;19:308–19.
334. Gerner EW. Ocular toxicity of tamoxifen. Ann Ophthalmol 1989;21:420–3.
335. Andersson M, Storm HH, Mouridsen HT. Incidence of new primary cancers
after adjuvant tamoxifen therapy and radiotherapy for early breast cancer. J
Natl Cancer Inst 1991;83:1013–7.
336. Wolf DM, Jordan VC. Gynecologic complications associated with long-term
adjuvant tamoxifen therapy for breast cancer. Gynecol Oncol 1992;45:118–28.
337. van Leeuwen FE, Benraadt J, Coebergh JW, Kiemeney LA, et al. Risk of
endometrial cancer after tamoxifen treatment of breast cancer [see
338. Arriagada R, Rutqvist LE. Adjuvant chemotherapy in early breast cancer and
incidence of new primary malignancies [see comments]. Lancet
1991;338:535–8.
339. Wickerham DL, Constantino JC, Fisher B, et al.The initial results from the
NSABP protocol P-1: a clinical trial to determine the worth of tamoxifen for
preventing breast cancer in women at increased risk. Proc Ann Meeting Am
Soc Clin Oncol 1998;17.
340. Smith DC, Prentice R, Thompson DJ, Herrmann WL. Association of
exogenous estrogen and endometrial carcinoma. N Engl J Med
1975;293:1164–7.
341. Antunes CMF, Stolley PD, Rosenheim Endometrial cancer and estrogen use
(report of a large case-control study). N Engl J Med 1979;300:9.
342. Osborne CK.Tamoxifen in the treatment of breast cancer. N Engl J Med
1998;339:1609–18.
343. Holli K. Adjuvant trials of toremifene versus tamoxifen: the European
experience. Oncology 1998;12:23–7.
344. Beatson GT. On the treatment of inoperable cases of carcinoma of the
mamma: suggestions for a new method of treatment, with illustrative cases.
Lancet 1896;1:104–7.
345. Boccardo F, Rubagott A, Amoroso D, et al. CMF versus tamoxifen plus
goserelin as adjuvant treatment of ER positive pre-perimenopausal breast
cancer patients. Proc Ann Meeting Am Soc Clin Oncol 1998;17.
346. Jakesz R, Hausmaninger H, Samonigg H, et al. Comparison of adjuvant
therapy with tamoxifen and goserelin Vs. CMF in premenopausal stage 1
and 2 hormone-responsive breast cancer patients: four year results of
Austrian Breast Cancer Study Group (ABCSG) Trial 5. Proc Am Soc Clin
Oncol 1999;18.
347. Davidson N, O’Neill A, Vukov A, et al. Effect of chemohormonal therapy in
premenopausal, node (+) breast cancer: an Eastern Cooperative Oncology
Group Phase 3 Intergroup Trial (E5188, INT-0101). Proc Am Soc Clin Oncol
1999;18.
348. Houghton J, Baum M, Rutvist L, et al.The ZIPP trial of adjuvant Zoladex in
premenopausal patients with early breast cancer: and update at 5 years.
Proc Am Soc Clin Oncol 2000;19.
349. Roche H, Kerbat P, Bardonnet M, et al. Complete hormonal blockade versus
chemotherapy in premenopausal early stage breast cancer patients (Pts)
with positive hormone receptor (HR+) and 1–3 node positive tumor (N+):
Results of the FASG 06 Trial. Proc Am Soc Clin Oncol 2000;19.
350. Ludwig Breast Cancer Study Group. Chemotherapy with or without
oophorectomy in high-risk premenopausal patients with operable breast
cancer. Ludwig Breast Cancer Study Group. J Clin Oncol 1985;3:1059–67.
351. Bonadonna G, Brusamolino E, Valagussa P, Rossi A, et al. Combination
chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J
Med 1976;294:405–10.
352. Colleoni M, Coates A, Pagani O, Goldhirsch A. Combined chemo-endocrine
adjuvant therapy for patients with operable breast cancer: still a question?
Cancer Treat Rev 1998;24:15–26.
353. Goldhirsch A, Glick JH, Gelber RD, Senn HJ. Meeting highlights: International
Consensus Panel on the Treatment of Primary Breast Cancer [see
354. Neville AM, Bettelheim R, Gelber RD, Save-Soderbergh J, et al. Factors
predicting treatment responsiveness and prognosis in node-negative breast
cancer. The International (Ludwig) Breast Cancer Study Group [see
comments]. J Clin Oncol 1992;10:696–705.
355. Fisher ER, Redmond C, Fisher B, Bass G. Pathologic findings from the
National Surgical Adjuvant Breast and Bowel Projects (NSABP). Prognostic
discriminants for 8-year survival for node-negative invasive breast cancer
patients. Cancer 1990;65:2121–8.
356. Coates A, Simes R. Patient assessment of adjuvant treatment in operable
breast cancer. In Williams C. Introducing new treatments for cancer:
practical, ethical and legal problems Chichester: John Wiley & Sons, 1993:
447–458.
357. Epstein RJ. Does the breast cancer dollar make sense? Eur J Cancer
1992;28:486–91.
358. Hillner BE, Smith TJ, Desch CE. Assessing the cost effectiveness of adjuvant
therapies in early breast cancer using a decision analysis model. Breast
Cancer Res Treat 1993;25:97–105.
359. Rubens RD. Management of early breast cancer [see comments]. BMJ
1992;304:1361–4.
360. O’Reilly SM, Richards MA. Node negative breast cancer [see comments].
BMJ 1990;300:346–8.
361. Glasziou P, Haas M. An economic evaluation of the use of tamoxifen in the
treatment of early breast cancer. 25. Sydney: Centre for Health Economic
Research and Evaluation (CHERE), 1994.
362. Simon MS, Hoff M, Hussein M, Martino S, Walt A. An evaluation of clinical
follow-up in women with early stage breast cancer among physician
members of the American Society of Clinical Oncology. Breast Cancer Res
Treat 1993;27:211–9.
363. Schapira DV. Breast cancer surveillance – a cost-effective strategy. Breast
Cancer Res Treat 1993;25:107–11.
364. Kennedy MJ, Abeloff MD. Management of locally recurrent breast cancer
[see comments]. Cancer 1993;71:2395–409.
365. Palli D, Russo A, Saieva C, Ciatto S, et al. Intensive vs clinical follow-up after
treatment of primary breast cancer: 10-year update of a randomized trial.
National Research Council Project on Breast Cancer Follow-up [letter;
comment]. JAMA 1999;281:1586.
366. The GIVIO Investigators. Impact of follow-up testing on survival and health-
related quality of life in breast cancer patients. A multicenter randomized
controlled trial. The GIVIO Investigators. JAMA 1994;271:1587–92.
367. Horn-Ross PL. Multiple primary cancers involving the breast. Epidemiol Rev
1993;15:169–76.
368. Kricker A, Hunt J, Smith C. Second primary breast cancer. NHMRC National
Breast Cancer Centre. Woolloomooloo (NSW): 1997.
369. Fallowfield LJ, Hall A. Psychosocial and sexual impact of diagnosis and
treatment of breast cancer. Br Med Bull 1991;47:388–99.
370. Levy SM, Haynes LT, Herberman RB, Lee J, et al. Mastectomy versus breast
conservation surgery: mental health effects at long-term follow-up [see
comments]. Health Psychol 1992;11:349–54.
371. Ward SE, Viergutz G, Tormey D, deMuth J, Paulen A. Patients’ reactions to
completion of adjuvant breast cancer therapy. Nurs Res 1992;41:362–6.
372. Polinsky ML. Functional status of long-term breast cancer survivors:
demonstrating chronicity [published erratum appears in Health Soc Work
1994 Nov;19(4):297]. Health Soc Work 1994;19:165–73.
373. Ferrans CE. Quality of life through the eyes of survivors of breast cancer
[published erratum appears in Oncol Nurs Forum 1995 Jan-Feb;22(1):14].
Oncol Nurs Forum 1994;21:1645–51.
374. Morris S, Corder AP, Taylor I. What are the benefits of routine breast cancer
follow-up? Postgrad Med J 1992;68:904–7.
375. Hall A, Fallowfield L, A’Hern R. When breast cancer recurs: a 3 year
prospective study of psychological morbidity. The Breast 1996;2:197–203.
376. Schapira DV, Urban N. A minimalist policy for breast cancer surveillance [see
comments]. JAMA 1991;265:380–2.
377. Grunfeld E, Mant D, Yudkin P, Adewuyi-Dalton R, et al. Routine follow up of
breast cancer in primary care: randomised trial [see comments]. BMJ
1996;313:665–9.
378. Davis C, Girgis A, Williams P, Beeney L. Needs assessment of rural and remote
women travelling to the city for breast cancer treatment. Aust N Z J Public
Health 1998;22:525–7.
379. Brushin B, Gonzalea M, Payne R. Exploring cultural attitudes to breast
cancer: towards the development of culturally appropriate information
resources for women from Greek, Italian, Arabic and Polish speaking
backgrounds. Woolloomooloo, NSW: NHMRC National Breast Cancer
Centre, 1997.
380. Carrick S, Clapham K, Paul Cea. Breast cancer and Aboriginal and Torres
Strait Islander women. Woolloomooloo, NSW: NHMRC National Breast
381. Australia, House of Representatives. Report on the management and
treatment of breast cancer in Australia. 1995.
382. National Health and Medical Research Council. A guide to the development
and implementation of clinical practice guidelines. Canberra: Australian
Government Printing Service, 1998.
383. Salkeld G, Easter S. The cost of diagnostic investigations for women
presenting with breast symptoms. Woolloomooloo, NSW: NHMRC National
Breast Cancer Centre, 1998.
384. Schwartz D, Flamant R, Lellouch J. Clinical Trials. London:Academic Press, 1980.
385. Tannock IF, Boyd NF, DeBoer G, Erlichman C, et al.A randomized trial of two
dose levels of cyclophosphamide, methotrexate, and fluorouracil
chemotherapy for patients with metastatic breast cancer [see comments]. J
Clin Oncol 1988;6:1377–87.
386. National Institutes of Health. Consensus development statement: adjuvant
therapy for breast cancer. 2000
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CLINIC AL PRACTICE GUIDELINES

CLINIC AL PRACTICE GUIDELINES

Prepared by the iSource National Breast Cancer Centre

Endorsed August 2001

Clinical practice guidelines for the management of early breast cancer i

• fostering and supporting a high quality and internationally recognised research

This document is a general guide to appropriate practice, to be followed only

The guidelines are designed to provide information to assist decision-making

It is planned to review this Clinical Practice Guideline by 2006. For further

ii Clinical practice guidelines for the management of early breast cancer

List of abbr eviation s ix

Impor tan t n otice xi

1. Th e clin ical pictur e 11

2. Gen er al pr in ciples of car e 21

3. Befor e defin itive tr eatmen t 41

6. Systemic adjuvan t th er apy 77

8. Requir emen ts for special gr oups 1 03

9. Ar eas w h er e r esear ch is n eeded 1 07

iv Clinical practice guidelines for the management of early breast cancer

Clinical practice guidelines for the management of early breast cancer v

Professor Christine Ewan

ADH atypical ductal hyperplasia

Clinical practice guidelines for the management of early breast cancer ix

x Clinical practice guidelines for the management of early breast cancer

This document is a guide to appropriate practice, to be followed subject to the

Clinical practice guidelines for the management of early breast cancer xi

These guidelines refer to breast cancer in the early stages, as it commonly

PURPOSE OF THE GUIDELINES

Clinical practice guidelines for the management of early breast cancer 1

First edition (1995)

2 Clinical practice guidelines for the management of early breast cancer

Clinical practice guidelines for the management of early breast cancer 3

The consumer version

4 Clinical practice guidelines for the management of early breast cancer

Clinical practice guidelines for the management of early breast cancer 5

The following table provides a summary of the guideline recommendations

Guidelines Level of References Chapter

COUNSELLING AND SUPPORT

2. Strategies to improve recall of information are

3. Counselling is recommended for women with I 120 2.3

PARTICIPATION IN CLINICAL TRIALS

SURGERY FOR INVASIVE BREAST CANCER

8. Where appropriate, women should be offered a I 195 4.3

9. For most women with early breast cancer, a

11. Postmastectomy radiotherapy is recommended I 269, 228 5.2

SYSTEMIC ADJUVANT THERAPY

13. Up to the age of 70 years, multi-agent I 298 6

8 Clinical practice guidelines for the management of early breast cancer

SYSTEMIC ADJUVANT THERAPY con’t

15. Anthracycline-containing regimes are superior to I 298 6.2

16. Dose intensity is important to outcome in II 311 6.2

17. Treatment with high-dose chemotherapy outside II 314, 315 6.2

19. Tamoxifen is recommended for most women with I 297 6.3

20. Tamoxifen reduces the incidence of contralateral I 297 6.3

21. Women should be informed of the potential side II 45–48 6.3

Clinical practice guidelines for the management of early breast cancer 9

SYSTEMIC ADJUVANT THERAPY con’t

24. Tamoxifen in combination with chemotherapy I 297 6.5

10 Clinical practice guidelines for the management of early breast cancer

Figure 1: Age-standardised incidence rates of breast cancer

Clinical practice guidelines for the management of early breast cancer 11

12 Clinical practice guidelines for the management of early breast cancer

Clinical practice guidelines for the management of early breast cancer 13